[ CAS No. 4286-55-9 ] {[proInfo.proName]}

Name: 4286-55-9|6-Bromohexan-1-ol|97%
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3d Animation Molecule Structure of 4286-55-9

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Quality Control of [ 4286-55-9 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 4286-55-9 ]

Product Details of [ 4286-55-9 ]

CAS No. :	4286-55-9	MDL No. :	MFCD00002983
Formula :	C₆H₁₃BrO	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	FCMCSZXRVWDVAW-UHFFFAOYSA-N
M.W :	181.07	Pubchem ID :	77970
Synonyms :

Calculated chemistry of [ 4286-55-9 ]

Physicochemical Properties

Num. heavy atoms :	8
Num. arom. heavy atoms :	0
Fraction Csp3 :	1.0
Num. rotatable bonds :	5
Num. H-bond acceptors :	1.0
Num. H-bond donors :	1.0
Molar Refractivity :	39.99
TPSA :	20.23 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.18 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.2
Log Po/w (XLOGP3) :	1.73
Log Po/w (WLOGP) :	1.93
Log Po/w (MLOGP) :	2.06
Log Po/w (SILICOS-IT) :	1.93
Consensus Log Po/w :	1.97

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	2.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-1.72
Solubility :	3.43 mg/ml ; 0.0189 mol/l
Class :	Very soluble
Log S (Ali) :	-1.77
Solubility :	3.07 mg/ml ; 0.0169 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-2.58
Solubility :	0.471 mg/ml ; 0.0026 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.54

Safety of [ 4286-55-9 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P305+P351+P338	UN#:	N/A
Hazard Statements:	H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 4286-55-9 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Upstream synthesis route of [ 4286-55-9 ]
Downstream synthetic route of [ 4286-55-9 ]

[ 4286-55-9 ] Synthesis Path-Upstream 1~17

1
[ 4286-55-9 ]
[ 123-31-9 ]
[ 18979-55-0 ]

Reference： [1] Chemical Communications, 2018, vol. 54, # 38, p. 4834 - 4837

2
[ 629-11-8 ]
[ 629-03-8 ]
[ 4286-55-9 ]

Reference： [1] Journal of Organic Chemistry, 2000, vol. 65, # 18, p. 5837 - 5838
[2] Chemistry and Physics of Lipids, 1994, vol. 71, # 2, p. 145 - 162

3
[ 1110667-72-5 ]
[ 629-03-8 ]
[ 4286-55-9 ]
[ 1110667-79-2 ]
[ 1110667-78-1 ]

Reference： [1] Synthesis, 2008, # 22, p. 3565 - 3568

4
[ 1110667-72-5 ]
[ 629-03-8 ]
[ 4286-55-9 ]
[ 1110667-78-1 ]

Reference： [1] Synthesis, 2008, # 22, p. 3565 - 3568

5
[ 1110667-75-8 ]
[ 629-03-8 ]
[ 53963-10-3 ]
[ 4286-55-9 ]
[ 1110667-79-2 ]

Reference： [1] Synthesis, 2008, # 22, p. 3565 - 3568

6
[ 1110667-76-9 ]
[ 629-03-8 ]
[ 4286-55-9 ]
[ 18173-64-3 ]
[ 129368-70-3 ]

Reference： [1] Synthesis, 2008, # 22, p. 3565 - 3568

7
[ 4286-55-9 ]
[ 105-53-3 ]
[ 764-89-6 ]

Reference： [1] Russian Journal of Bioorganic Chemistry, 2008, vol. 34, # 1, p. 67 - 73

8
[ 4286-55-9 ]
[ 124-38-9 ]
[ 3710-42-7 ]

Reference： [1] Journal of the American Chemical Society, 2014, vol. 136, # 32, p. 11212 - 11215

9
[ 4286-55-9 ]
[ 536-90-3 ]
[ 1810-74-8 ]

Reference： [1] Acta Crystallographica Section C: Crystal Structure Communications, 1998, vol. 54, # 7, p. 978 - 980

10
[ 4286-55-9 ]
[ 6294-17-3 ]

Reference： [1] Journal of Organic Chemistry, 1994, vol. 59, # 9, p. 2616 - 2619

11
[ 4286-55-9 ]
[ 89359-54-6 ]

Reference： [1] Patent: WO2015/181116, 2015, A1,

12
[ 4286-55-9 ]
[ 4224-70-8 ]

Reference： [1] Angewandte Chemie - International Edition, 2002, vol. 41, # 21, p. 4059 - 4061
[2] Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 2, p. 605 - 611
[3] Journal of the American Chemical Society, 1950, vol. 72, p. 5137
[4] Tetrahedron Asymmetry, 2003, vol. 14, # 13, p. 1799 - 1806
[5] Angewandte Chemie - International Edition, 2002, vol. 41, # 21, p. 4059 - 4061

13
[ 6066-82-6 ]
[ 4286-55-9 ]
[ 4224-70-8 ]
[ 42014-54-0 ]

Reference： [1] Angewandte Chemie - International Edition, 2002, vol. 41, # 21, p. 4059 - 4061

14
[ 4286-55-9 ]
[ 996-82-7 ]
[ 17696-11-6 ]

Reference： [1] Journal of the Chemical Society, 1961, p. 4409 - 4412

15
[ 4286-55-9 ]
[ 1633-78-9 ]

Yield	Reaction Conditions	Operation in experiment
75%	With thiourea; sodium hydroxide In 1,4-dioxane at 80℃;	6-Bromohexanol (1 g, 5.60 mmol) was allowed to reflux withthiourea (0.64 g, 8.40 mmol) and NaOH (0.1 M) in 1,4-dioxane (4 mL) for 4 h. The reaction mixture was cooledand the solvent was removed under vacuum. The pH of thereaction mixture was adjusted to 4 by adding dilute. HCl andthe thiol derivative was extracted using dichloromethane. Theorganic layerwas dried overNa2SO4 and concentrated to give6-mercaptohexanol as an yellow oil.Yield: 0.563 g (75percent); 1H NMR (500 MHz, DMSO-d6,TMS): δ 3.65 (s, 1H), 3.5 (t, 2H, J = 2.4Hz), 2.56 (t, 2H,J = 2.3Hz), 1.52–1.57 (m, 4H), 1.5 (s, 1H), 1.41–1.44 (m,4H); 13C NMR (125 MHz, DMSO): δ 62.8, 34.5, 32.3, 28.2,24.9, 24.6; ESI–MS:m/z Calcd. forC6H14OS: 134.08, Found:135.11 (M+ + 1).

Reference： [1] Journal of Chemical Sciences, 2018, vol. 130, # 10,
[2] Journal of Organic Chemistry, 1999, vol. 64, # 13, p. 4959 - 4961
[3] Chemical Physics Letters, 1997, vol. 264, # 3-4, p. 376 - 380
[4] Chemistry Letters, 1996, # 8, p. 635 - 636
[5] Chemistry Letters, 1996, # 8, p. 635 - 636
[6] Canadian Journal of Chemistry, 2012, vol. 90, # 1, p. 145 - 152
[7] Chemical Communications, 2013, vol. 49, # 84, p. 9821 - 9823

16
[ 4286-55-9 ]
[ 50889-29-7 ]

Reference： [1] Tetrahedron Asymmetry, 2003, vol. 14, # 13, p. 1799 - 1806

17
[ 4286-55-9 ]
[ 83883-26-5 ]

Reference： [1] Macromolecules, 2003, vol. 36, # 24, p. 9060 - 9066
[2] Chemistry Letters, 1994, # 3, p. 557 - 560
[3] Molecular Crystals and Liquid Crystals (1969-1991), 1988, vol. 155, p. 113 - 128
[4] Reactive and Functional Polymers, 2010, vol. 70, # 4, p. 217 - 222
[5] Journal of Materials Chemistry C, 2015, vol. 3, # 18, p. 4663 - 4669

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Yield	Reaction Conditions	Operation in experiment
98%	With hydrogen bromide In water; toluene for 2h; Heating / reflux;
98%	With hydrogen bromide In water; toluene at 120℃; for 72h;
97%	With hydrogen bromide In benzene Heating;

94%	With hydrogen bromide In toluene for 12h; Reflux;	6-Bromo-1-hexanol (9) To a mixture of diol 8 (15.15 g, 0.13 mol, 1 eq) and toluene (350 mL) was addedconcentrated hydrobromic acid (aq. 48%, 17.26 mL, 0.15 mol, 1.2 eq). The heterogeneousmixture was stirred and heated at reflux for 12 h, with a flat balloon fitted on top of thecondenser. TLC analysis indicated that substantial amounts of diol still remained. Thus, afurther quantity of hydrobromic acid (4.35 mL, 0.03 mol, 0.3 eq) was added, and the mixturewas heated at reflux overnight, at which time TLC analysis showed little diol 8 remaining.The reaction mixture was allowed to cool to room temperature, and the phases were separated. The organic layer was diluted with ether and washed with 1M NaOH and brine.Drying over anhydrous Na2SO4 and concentration of the organic layer in vacuo gave a yellowoil which was purified by column chromatography (Et2O/petrol 1:1) to give 21.65 g (94%)product 9 as a colourless oil.
90%	With hydrogen bromide In water; toluene for 12h; Reflux;
87%	With hydrogen bromide In toluene at 110℃; for 24h;	General procedure for the synthesis of methanesulfonatealkylazides (4a, 4b, and 4d) General procedure: To a stirred solution of 1,6-hexanodiol 1a (1.00 equiv.), 1,9-nonanediol 1b (1.00 equiv.), or 1,12-dodecanediol 1c (1.00 equiv.), in 30 mL of toluene was added HBr 48 % (2.00 equiv.). The reaction was stirred at 110 °C for 24 h. The solvent was removed under reduced pressure, and the residue was purified by column chromatography over silica gel, eluting with hexane/EtOAc 9:1, to yield pure haloalcohol 2a-c. These compounds were transformed into their corresponding azido alcohols 3a-c by SN2 substitution (Scheme 1). A stock solution of 0.5 M NaN3 in DMSO was prepared by stirring the solution for 24 h at room temperature. To a 100-mL round-bottom flask equipped with a magnetic stir bar was added a 0.5 M solution of NaN3 in DMSO at room temperature. To this solution was added the bromo alcohol 2a (1.00 equiv.), 2b (1.00 equiv.), or 2c (1.00 equiv.), and the mixture was stirred for 24 h at room temperature.The reaction was quenched with H2O (50 mL) and stirred until it cooled to room temperature. The mixture was extracted with Et2O (3 9 30 mL), and the resulting extracts were washed with H2O (3 x 50 mL) and brine (50 mL). The organic layer was dried (Na2SO4) and filtered, and the residue obtained was purified by column chromatography over silica gel, eluting with hexane/EtOAc 9:1, to yield pure alkyl azido alcohols 3a-c. A solution of the azido alcohol 3a (1.00 equiv.), 3b (1.00 equiv.), or 3c (1.00 equiv.) in CH2Cl2 (50 mL) was cooled to 0 °C. Et3N (2.00 equiv.) and methanesulfonyl chloride (2.00 equiv.) was added. The reaction mixture was stirred for 24 h and then allowed to reach room temperature. The reaction mixture was poured into crushed ice (70 mL) and was then extracted with methylene chloride (3 9 30 mL). The organic layer was dried (Na2SO4), filtered, and evaporated under reduced pressure. The residue obtained was purified by column chromatography over silica gel, eluting with hexane/EtOAc 9:1, to yield highly purified halo alcohol pure methanesulfonate alkyl azides compounds 4a, 4b, and 4d.
86%	With hydrogen bromide In n-heptane Heating;
86.8%	With hydrogen bromide In water; toluene for 18h; Inert atmosphere; Reflux;
85%	With hydrogen bromide In benzene for 28h; Heating;
84%	With hydrogen bromide In water; toluene for 72h; Reflux;
83%	With hydrogen bromide In water; toluene for 18h; Dean-Stark; Reflux;
81%	With hydrogen bromide In water for 24h; Heating;
80%	With hydrogen bromide for 24h; Heating;
79%	With hydrogen bromide
78%	With hydrogen bromide In water for 48h; Reflux;	Synthesis of compound 4 Synthesis of compound 4 4 1 ,6-Hexanodiol (50 g, 0.423 mol) was disolved in 120 ml of 48% aqueous HBr and heated at reflux for 48 h with continuous extraction with toluene (250 ml). The organic phase was washed with saturated Na2C03 solution and with NaCI and then dried over anhydrous MgS04, filtered and evaporated to dryness. The resulting product was distilled under vacuum (96°C / 1 mm Hg) to yield a colorless liquid (60 g, 78%).
75%	With hydrogen bromide In toluene at 80℃; for 24h;	1.i i) Preparing 6-bromo-1-hexanol.Putting 1,6-hexanediol (20 g) and 48% (wt %) HBr into a reacting bottle (500 mL), adding toluene (200 mL) followed by stirring and refluxing at 80° C. for 24 hours. Then cooling to the room temperature, removing the solvent by a rotary vacuum evaporator, drying with anhydrous magnesium sulfate to gain crude product, wherein column chromatography of the crude product is carried out to gain pure 6-bromo-1-hexanol (22.85 g). The yield is about 75%.
75%	With tetrabutylammomium bromide; hydrogen bromide In water for 0.0833333h; Microwave irradiation;
74%	With hydrogen bromide In water; toluene for 3h; Reflux;
73%	With hydrogen bromide In water; toluene at 80℃; for 20h;	4 5.3.4. 1-Bromohexanol (6) To a stirred solution of 1,6-hexanediol (6.0 g, 1 eq.) in toluene, HBr (7 ml, 9 M, 1.3 eq.) was added and allowed to react at 80 °C for 20 h. Then the reaction mixture was extracted with Et2O (×3), the combined extracts dried over Na2SO4, filtered, and the solvent was removed under reduced pressure. The resulting liquid was purified by CC using hexane:Et2O (1:1) as mobile phase. From this, 1-bromohexanol was obtained (7.073 g, 73% yield). 1H NMR (300 MHz, CDCl3): δ 3.63 (2H, t, J = 6.6 Hz, CH2Br), 3.40 (2H, t, J = 6.6 Hz, HOCH2), 1.86 (2H, q, J = 7.2, CH2CH2Br), 1.20-1.60 (6H, m, aliphatic CH).
72%	With hydrogen bromide In water; toluene for 48h; Reflux; Inert atmosphere;
70%	With hydrogen bromide at 70℃; for 50h;
70%	With hydrogen bromide In benzene for 23h; Heating;
70%	With hydrogen bromide In water; benzene for 72h; Heating;
69.3%	With hydrogen bromide In cyclohexane; water at 80℃; for 5h; Inert atmosphere;
65%	With hydrogen bromide for 2h; Heating;
60%	With hydrogen bromide In benzene for 18h; Heating;
60%	With hydrogen bromide In toluene for 48h; Reflux;	1; 7 EXAMPLE 7 6-Bromo-1-hexanol (2) 1,6-hexandiol (1) (35.6 g, 0.3 mol), hydrobromic acid (aq. 48%, 51 g, 0.3 mol) and toluene (100 mL) were mixed in a round-bottom flask equipped with a Dean-Stark trap. The mixture was heated under reflux with stirring over two days. After that, the mixture was concentrated and subjected to flash chromatography using petroleum ether 100% followed by petroleum ether : dichloromethane (1:1 v/v) and finally dichloromethane 100% as a mobile phase to give 6-bromo-1-hexanol (2) as a pale yellow liquid (32.4 g, 60%). 1H-NMR (CDCl3) : 3.66 (t, 2H, CH2OH, J=6.4 Hz), 3.40 (t, 2H, BrCH2, J=6.7 Hz), 2.5 (brs, 1H, OH), 1.86 (m, 2H, CH2), 1.30-1.70 (m, 6H, CH2). 13C-NMR CDCl3): 62.9, 33.9, 32.7, 32.4, 28.0 and 25.0.
60%	With hydrogen bromide In benzene for 18h; Reflux; Dean-Stark; Inert atmosphere;
60%	With hydrogen bromide In water; toluene Reflux; Dean-Stark;
56%	With hydrogen bromide In toluene at 75 - 80℃; for 39h;
50%	With hydrogen bromide In water; Petroleum ether for 9h; Heating;
46%	With hydrogen bromide at 90℃; for 72h;
45%	With hydrogen bromide In toluene at 120℃; for 24h;
45%	With hydrogen bromide In water for 1h; Reflux;
42%	With sulfuric acid; hydrogen bromide In water for 2h; Heating;
	With water; hydrogen bromide
	With Pyridine hydrobromide for 2h; Heating;
	With hydrogen bromide at 80℃; for 48h;
	With hydrogen bromide In benzene Heating;
	With hydrogen bromide at 100℃;
	In n-heptane; hydrogen bromide
	With hydrogen bromide
	With hydrogen bromide In toluene Heating;
	With hydrogen bromide In toluene Heating;
	With sulfuric acid; hydrogen bromide for 2h; Heating;
	With hydrogen bromide In benzene Heating;
	With hydrogen bromide at 80℃; for 40h;
	With hydrogen bromide In toluene Heating;
	With hydrogen bromide In water; toluene Reflux;
	With hydrogen bromide In water; toluene
	With hydrogen bromide In ligroin; water; toluene for 24h; Reflux;
	With hydrogen bromide In water
	With hydrogen bromide In water; toluene for 72h; Reflux;
	With hydrogen bromide In water; toluene for 48h; Reflux;
	Multi-step reaction with 3 steps 1: pyridine / dichloromethane / 8 h / 0 °C 2: triphenylphosphine; carbon tetrabromide / dichloromethane / 24 h / 0 - 20 °C 3: methanol; 2-Chloroethyl chloroformate
	With carbon tetrabromide; triphenylphosphine In tetrahydrofuran; dichloromethane
	With hydrogen bromide In toluene for 75h; Reflux;
	With hydrogen bromide In water; toluene for 24h; Reflux;

Yield	Reaction Conditions	Operation in experiment
91%	With 2-hydroxypyridin; 1-hydroxy-3H-benz[d][1,2]iodoxole-1,3-dione In dimethyl sulfoxide at 20℃; for 72h;
80%	Stage #1: 1-bromo-6-hexanol With sodium hypochlorite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; tetrabutylammomium bromide; sodium hydrogencarbonate In water; ethyl acetate at 0℃; Stage #2: With hydrogenchloride In water
	With nitric acid zuletzt unter Erhitzen;

Yield	Reaction Conditions	Operation in experiment
100%	With dimethylsulfide borane complex
98%	With dimethylsulfide borane complex In tetrahydrofuran at 0℃;
97%	With dimethylsulfide borane complex In tetrahydrofuran at 45℃; for 1h; Cooling with ice;	3.1.2. General Procedure for the Synthesis of Alcohols 4-6 General procedure: To an ice-cold solution of acid 1-3 (20 mmol) in THF (30 mL), a borane dimethylsulphide complex (2.7 mL, 28 mmol) was added dropwise. The solution was warmedat room temperature and stirred for 1 h at 45 C. Then, the reaction was cooled at 0 C,quenched with MeOH (60 mL) and concentrated under reduced pressure. The residuewas dissolved in EtOAc, washed with brine, dried over Na2SO4 and concentrated invacuo to obtain the projected alcohols 4-6, which were used in the next step withoutfurther purification.

[ CAS No. 4286-55-9 ] {[proInfo.proName]}

Quality Control of [ 4286-55-9 ]

Related Doc. of [ 4286-55-9 ]

Product Details of [ 4286-55-9 ]

Calculated chemistry of [ 4286-55-9 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 4286-55-9 ]

Application In Synthesis of [ 4286-55-9 ]

[ 4286-55-9 ] Synthesis Path-Upstream 1~17

[ 4286-55-9 ] Synthesis Path-Downstream 1~88

Related Functional Groups of
[ 4286-55-9 ]

Aliphatic Chain Hydrocarbons

Bromides

Alcohols

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Inquiry

	With jones reagent In acetone at 0 - 20℃;
	Multi-step reaction with 2 steps 1: 1-hydroxy-1,2-benziodoxole-3(1H)-one-1-oxide / dimethylsulfoxide / 16 h / 20 °C 2: NaOH; H₂O / dimethylsulfoxide

94.2%	With borane-THF In tetrahydrofuran at 25℃; for 0.5h;
	With borane In tetrahydrofuran
	With sodium tetrahydroborate; N,N-dimethylchloromethyleniminium chloride 1.) acetonitrile, THF, -30 deg C, 1 h; 2.) acetonitrile, THF, N,N-dimethylformamide, -78 deg C to -20 deg C, 2 h; Yield given. Multistep reaction;
	With tetrafluoroboric acid-diethyl ether complex In tetrahydrofuran

Yield	Reaction Conditions	Operation in experiment
100%	With DL-10-camphorsulphonic acid In dichloromethane at 0℃; for 2h;
100%	With pyridinium p-toluenesulfonate In dichloromethane at 20℃; for 3h;
98%	With pyridinium 4-toluenesulfonate In dichloromethane for 5h;	1.A 1-Tetrahydropyranyloxy-6-bromohexane (p=4) A solution of commercially available bromoalcohol (27.6 mmol), dihydropyran (2.57 g, 30.6 mmol), and pyridinium p-toluenesulfonate (PPTS) (10 mg, 0.04 mmol) in dichloromethane (DCM, 50 mL) was stirred for 5 h under nitrogen. Afterwards, sodium bicarbonate (NaHCO3, 500 mg) and MgSO4 (5.0 g) were added to the reaction mixture and stirred 15 minutes before being filtered on a short pad of celite/silica gel (1 cm/4 cm) using DCM as the eluent. The filtrate was evaporated to a viscous oil (98% yield), which was used without further purification in the next step. [0104] 1-Tetrahydropyranyloxy-6-bromohexane (p=4) [0105] IR (NaCl, νmax, cm-1): 1170-1000 (C-O). [0106] 1H-NMR (CDCl3, δ ppm): 4.57 (1H, t, J=3.2 Hz, OCHO), 3.87, 3.74, 3.50, and 3.38 (4H, 4 m, CH2OCHOCH2), 3.41 (2H, t, J=6.7 Hz, CH2Br), 1.3-2.0 (14H, No.m, 7×CH2). [0107] MS (m/e): 265 (M++1), 163 (M+-OTHP).

98%	With pyridinium 4-toluenesulfonate In dichloromethane at 20℃; for 4h; Inert atmosphere;
97%	With pyridinium 4-toluenesulfonate In dichloromethane at 20℃; for 23h;
96.4%	With toluene-4-sulfonic acid In dichloromethane at 20℃;	Synthesis of compounds 1-5 General procedure: 3,4-Dihydropyran (DHP, 15 mmol) was added slowly to a stirred solution of bromohydrin (10 mmol) and p-toluenesulfonic acid (1 mmol) in dichloromethane (20 mL) on ice bath. After stirring at room temperature overnight, the reaction mixture was diluted with water and extracted with dichloromethane. The organic layer was washed with brine and dried over anhydrous Na2SO4. The solvent was evaporated under reduced pressure, and the residue was purified by flash column chromatography to afford 1-5 as a light yellow oil.
95%	With toluene-4-sulfonic acid In diethyl ether for 12h; Ambient temperature;
95%	With pyridinium 4-toluenesulfonate In dichloromethane for 3h; Ambient temperature;
95%	With trifluoroacetic acid In dichloromethane
95%	With (1S)-10-camphorsulfonic acid In diethyl ether at 20℃;	3.1.12. 6-(1-Heptyl-1H-1,2,3-triazol-4-yl)hexanoic acid (14) (Scheme 3) General procedure: 3,4-Dihydro-2H-pyran (1.40g, 16.0mmol) was added to stirred solution of 6-bromo-1-hexanol (33a) (2.0g, 11.0mmol) and camphorsulfonic acid (116mg, 5mol%) in Et2O at room temperature overnight. The reaction was basified with satd K2CO3 and extracted into Et2O, washed with brine and dried over Na2SO4. Purification by flash column chromatography; neat CH2Cl2 gave 2-((6-bromohexyl)oxy)tetrahydro-2H-pyran (34a) (2.70g, 95%) as a colourless oil. 1H NMR [DMSO] δ 4.55-4.50 (m, 1H), 3.72 (ddd, J=11.2, 8.1, 3.1Hz, 1H), 3.61 (td, J=9.7, 6.7Hz, 1H), 3.52 (t, J=6.7Hz, 2H), 3.46-3.37 (m, 1H), 3.35-3.28 (m, 1H), 1.84-1.76 (m, 2H), 1.73-1.64 (m, 1H), 1.64-1.54 (m, 1H), 1.54-1.28 (m, 10H). HRMS (ESI+) Calcd for C11H21BrNaO2: 287.0617; (MNa+) 287.0613n-Butyllithium (2.07mL of a 2.0M solution in cyclohexanes, 4.1mmol) was added dropwise to a solution of trimethylsilylacetylene (0.60mL, as a solution in THF, 4.1mmol) in THF (8mL) at -60°C, then the reaction was allowed to warm to 0°C for 30min.12 The reaction was then cooled to -20°C, HMPA (2mL) was added dropwise followed by 34a (1.0g, 3.8mmol). The reaction was stirred for 5h at 0°C and room temperature for an additional 14h, then quenched with satd NH4Cl and extracted into EtOAc, washed with brine and dried over Na2SO4. The crude oil was filtered through a pad of silica with CH2Cl2 and concentrated to dryness to give (by 1H NMR) a 2:1 mixture of trimethyl-(8-((tetrahydro-2H-pyran-2-yl)oxy)oct-1-yn-1-yl)silane (35a) and 2-(oct-7-yn-1-yloxy)tetrahydro-2H-pyran (36a) (1.0g, 98%). This (1.0g, 3.8mmol) was taken up in THF (10mL) and stirred with TBAF (5.6mL as a 1molL-1 solution in THF, 5.6mmol) at room temperature for 48h. The reaction was diluted with EtOAc, and washed with satd NaHCO3, brine, dried over Na2SO4 and concentrated to dryness to give only 36a (740mg, 91%) as a colourless oil.
95%	With toluene-4-sulfonic acid In dichloromethane at 0 - 20℃; for 16h; Inert atmosphere;	16 4.1.16 2-(6-Bromohexyl-1-oxy)tetrahydropyran 24 To a stirred solution of 6-bromohexyl-1-ol 23 (2.0 g, 9.61 mmol) in anhydrous CH2Cl2 (40 mL) at 0 °C, under N2, DHP (1.051 mL, 11.53 mmol) and PTSA (603 mg, 2.40 mmol) were added. The reaction mixture was allowed to stir for 16 h in the water bath, under N2 atmosphere, by which time the solution had turned slightly brown in color. After completion, the reaction mixture was neutralized with aqueous NaHCO3 (50 mL), the organic phase was collected and the aqueous phase re-extracted with CH2Cl2 (2 * 30 mL). Organic fractions were combined, washed with water (30 mL), brine (30 mL) over MgSO4, filtered and concentrated to a crude residue. This crude residue was purified by silica gel (60-120) flash column chromatography, eluting with hexane/EtOAc (9:0.5 v/v), to furnish 24 as a bright yellow oil (2.5 g, 95%): Rf 0.60 (hexane/EtOAc, 9:1 v/v). 1H NMR (400 MHz, CDCl3): δ 1.31-1.62 (m, 10H 5*CH2), 1.66-1.71 (m, 1H CH2), 1.88-2.0 (m, 3H), 3.37-3.48 (m, 3H), 3.50-3.54 (m, 1H), 3.72-3.75 (m, 1H, CHO), 3.85-3.87 (m, 1H, CHO), 4.57-4.59 (t, 1H, CHO); ESI+, m/z 264 [M+H]+.
94%	With 1-n-butyl-3-methylimidazolium hydrogen sulfate for 0.0333333h; microwave irradiation;
93%	With Amberlyst-15(Cat) In dichloromethane at 20℃; Inert atmosphere;	Synthesis of Compound 2 Under argon protection, 6-bromo-1-hexanol (39.82 g, 0.22 mol) was dissolved in dry dichloromethane (250 mL), a catalytic amount of Amberlyst-15 ion exchange resin (0.6 g) was added, and at room temperature 3,4-dihydropyrane (18.7 g, 0.22 mol) was slowly added drop wise , and detected by TLC, after the reaction was completed, it was filtered, concentrated, and the crude product was subjected to column chromatography to give 54.1 g of a colorless transparent liquid, yield was 93%.
92%	With toluene-4-sulfonic acid In dichloromethane for 16h; Ambient temperature;
92%	With pyridinium 4-toluenesulfonate In dichloromethane at 20℃; for 5h;
92%	With toluene-4-sulfonic acid In dichloromethane at 20℃;
90.9%		W.1.1 Step 1: Step 1: Synthesis of 6-bromo-1-(tetrahydropyranyloxy)hexane 197.8 g (1.09 mol) 6-bromo-1-hexanol were given into a 500 ml reactor vessel and cooled to 5 ØC or less. 102.1 g (1.21 mol) dihydropyran were added dropwise to this at a temperature of 10ØC or less. After dropping was finished, the mixture was returned to room temperature and stirred for one hour. The precipitate obtained in the reaction was purified in a silica gel column with hexane / IPE (diisopropyl ether) = 5 / 1, resulting in 263.4 g of 6-bromo- 1 -(tetrahydropyranyloxy)hexane. The yield was 90.9%.
90%	With o-toluenesulfonic acid In tert-butyl methyl ether at 0 - 3℃;	2-(6-Bromo-hexyloxy)-tetrahydro-pyran (XX)Bromohexanol (54.67 g) is dissolved in TBME (250 ml.) and dried over Na2SC>4. After filtration, TsOH (0.6 mmol) is added and the solution is cooled in an ice bath. 3,4-Dihydropyran (394 mmol) is added dropwise, while maintaining the temperature around 2-30C. After complete addition the reaction mixture is allowed to reach ambient temperature overnight. The mixture is ished with sat. NaHCC>3 (2 x 200 ml_). The aqueous layer is extracted with TBME (200 ml.) and the combined organic layers are ished with brine (200 ml_). After drying over Na2SC>4 (containing some K2CO3), the solvent is evapo- rated to yield (XX) as a colourless oil (90 %), which is stored at 4 0C over K2CO3 and is used without further purification.
90%	With toluene-4-sulfonic acid In tert-butyl methyl ether at 0 - 20℃;	2-(6-Bromo-hexyloxy)-tetrahydro-pyran (XX) Bromohexanol (54.67 g) is dissolved in TBME (250 mL) and dried over Na2SO4. After filtration, TsOH (0.6 mmol) is added and the solution is cooled in an ice bath. 3,4-Dihydropyran (394 mmol) is added dropwise, while maintaining the temperature around 2-3° C. After complete addition the reaction mixture is allowed to reach ambient temperature overnight. The mixture is ished with sat. NaHCO3 (2*200 mL). The aqueous layer is extracted with TBME (200 mL) and the combined organic layers are ished with brine (200 mL). After drying over Na2SO4 (containing some K2CO3), the solvent is evaporated to yield (XX) as a colourless oil (90%), which is stored at 4° C. over K2CO3 and is used without further purification.
90%	With pyridinium 4-toluenesulfonate In dichloromethane at 20℃; for 18h;
89%	With trichlorophosphate In diethyl ether 1.) 0 deg C, 30 min, 2.) RT, 2 h;
89%	With toluene-4-sulfonic acid In diethyl ether for 0.5h;
89%	With hydrogenchloride In diethyl ether at 0 - 20℃; for 14h;
87%	With pyridinium 4-toluenesulfonate In dichloromethane 1.) 0-5 deg C, 0.5 h, 2.) RT, 4 h;
87%	With iron(III) perchlorate In diethyl ether at 20℃; for 1.5h;
86.9%	With pyridinium 4-toluenesulfonate In dichloromethane at 20℃; for 3h;	16.1 Step (1) To a solution of 6-bromohexan-l-ol (10 g, 55.2 mmol) and 3,4-dihydro-2H-pyran (4.78 g,56.9 mmol) in DCM (150 mL) was added PPTS (1.61 g,6.41 mmol) then stirred at room temperature for 3 h. TLC (EA/PE 9/1, SM Rf: 0.2; product, Rf: 0.7) indicated that all the starting materials was consumed. The solvent was concentrated and purified by flash chromatography column (0-10% EA in PE (5%) to give 2-(6-bromohexoxy)tetrahydropyran (12.72 g, 48 mmol, 86.9% yield) as colorless oil. 1H NMR (500 MHz, CDCI3) d 4.60 - 4.53 (m, 1H), 3.90 - 3.83 (m, 1H), 3.77 - 3.71 (m, 1H), 3.53 - 3.47 (m, 1H), 3.44 - 3.35 (m, 3H), 1.93 - 1.79 (m, 3H), 1.76 - 1.67 (m, 1H), 1.65 - 1.36 (m, 10H).
86.9%	With pyridinium 4-toluenesulfonate In dichloromethane at 20℃; for 3h;	16.1 Step (1) To a solution of 6-bromohexan-l-ol (10 g, 55.2 mmol) and 3,4-dihydro-2H-pyran (4.78 g,56.9 mmol) in DCM (150 mL) was added PPTS (1.61 g,6.41 mmol) then stirred at room temperature for 3 h. TLC (EA/PE 9/1, SM Rf: 0.2; product, Rf: 0.7) indicated that all the starting materials was consumed. The solvent was concentrated and purified by flash chromatography column (0-10% EA in PE (5%) to give 2-(6-bromohexoxy)tetrahydropyran (12.72 g, 48 mmol, 86.9% yield) as colorless oil. 1H NMR (500 MHz, CDCI3) d 4.60 - 4.53 (m, 1H), 3.90 - 3.83 (m, 1H), 3.77 - 3.71 (m, 1H), 3.53 - 3.47 (m, 1H), 3.44 - 3.35 (m, 3H), 1.93 - 1.79 (m, 3H), 1.76 - 1.67 (m, 1H), 1.65 - 1.36 (m, 10H).
85%	With trifluoroacetic acid at 20℃; for 12h;
85%	With iodine In tetrahydrofuran for 0.05h; microwave irradiation;
85%	With pyridinium 4-toluenesulfonate In dichloromethane
84%	With hydrogen cation In diethyl ether
83%	With toluene-4-sulfonic acid In dichloromethane at 0 - 20℃; Inert atmosphere;
82%	With pyridinium 4-toluenesulfonate In dichloromethane at 20℃; for 1h;	2 EXAMPLE 2 First, 2-(6-bromohexyloxy)-tetrahydro-2H-pyran (compound (1 B-1)) was synthesized according to the following equation. [Show Image] Into a 500 ml eggplant-shaped flask, 25 g (0.139 mol) of 6-bromohexanol, 12.83 g (0.152 mol) of dihydropyran, 1.74 g (0.007 mol) of pyridinium paratoluenesulfonate and 300 ml of dichloromethane were put, and such a mixture was stirred for 1 hour at room temperature. After reaction was completed, a reaction solvent was removed by distillation by a rotary evaporator, and 30 g of a transparent liquid of 2-(6-bromohexyloxy)-tetrahydro-2H-pyran (1 B-1) was obtained by distillation. The yield was 82%. Next, using the compound (1 B-1), trans-4-(4-(6-(tetrahydro-2H-pyran-2-yloxy)hexyloxy)phenyl)cyclohexanol (1 B-2) was synthesized according to the following equation. [Show Image] A reflux tube was attached to a 300 ml eggplant-shaped flask, 3 g (0.015 mol) of trans-(4-hydroxycyclohexyl)phenol, 10.8 g (0.078 mol) of potassium carbonate, 0.26 g (0.0016 mol) of potassium iodide, 50 ml of acetone and 4.97 g (0.016 mol) of compound (1B-1) were put into the flask, and such a mixture was stirred for 24 hours in a state that it was refluxed with heating. After reaction was completed, a reaction solvent from which solid state content was removed by filtering was distilled by a rotary evaporator, and the reacted product was purified by a silica gel column chromatography (development solvent:hexane/ethyl acetate=3:1). As a result, 5.6 g of compound (1B-2) was obtained as a white solid material. The yield was 95%. Next, using the compound (1B-1) and compound (1B-2), trans-2-(6-(4-(4-(6-(tetrahydro-2H-pyran-2-yloxy)hexyloxy)phenyl)cyclohexyloxy)hexyloxy)tetrahydro-2H-pyran (1B-3) was synthesized according to the following equation. [Show Image] A reflux tube was attached to a 100 ml eggplant-shaped flask, and in a nitrogen atmosphere, 2 g (0.0053 mol) of compound (1B-2), 20 ml of tetrahydrofuran and 2 ml of hexamethyl phosphoric acid triamide were put into the flask. Further, 0.85 g (0.021 mol) of sodium hydroxide (60% assay) was gently added, and such a mixture was stirred for 30 minutes in a state that it was refluxed with heating. Thereafter, 5.07 g (0.019 mol) of compound (1 B-1) was added, and they were further stirred for 24 hours in a state that they were refluxed with heating. After reaction was completed, 10 ml of a saturated ammonium chloride aqueous solution was added to the reacted mixture, and 50 ml of a saturated saline solution was added, and an extraction was carried out with 200 ml of ethyl acetate. An organic layer obtained was dried by using sodium sulfate anhydride, a solvent was removed by distillation by a rotary evaporator, and the reminder was purified by a silica gel column chromatography (development solvent:hexane/ethyl acetate/dichloromethane=4:1:0.5). As a result, 2.31 g of compound (1 B-3) was obtained with an yield of 78%, Next, using the compound (1 B-3), trans-6-(4-(4-(6-hydroxyhexyloxy)phenyl)cyclohexyloxy)hexan-1-ol (1B-4) was synthesized according to the following equation. [Show Image] In a 100 ml eggplant-shaped flask, 2.31 g (0.0041 mol) of compound (1 B-3), 20 ml of methanol and 0.08 g (0.0004 mol) of paratoluene sulfonic acid monohydrate were added, and such a mixture was stirred for 2 hours at room temperature. After reaction was completed, a few drops of saturated sodium hydrogencarbonate aqueous solution was dropped, reaction solvent was removed by distillation by a rotary evaporator, and the reminder was purified by a silica gel column chromatography (development solvent:hexane/ethyl acetate=1:1). As a result, 1.19 g of compound (1B-4) was obtained with an yield of 74%. Next, using the compound B4, a compound (1 B) was synthesized according to the following equation. [Show Image] 1.19 g (0.00303 mol) of compound (1B-4), 0.04 g (0.0003 mol) of 4-dimethylaminopyridine, 20 ml of dichloromethane and 0.67 g (0.0067 mol) of triethylamine were added, 0.6 g (0.0067 mol) of acrylic acid chloride was slowly dropped at 0°C, and they were stirred for 1 hour at room temperature. To such a stirred mixture, 50 ml of a saturated saline solution was added, and extraction was carried out with 100 ml of dichloromethane. An organic layer obtained was dried with sodium sulfate anhydride, the solvent was removed by distillation by a rotary evaporator, and the reminder was purified by a silica gel column chromatography (development solvent:hexane/ethyl acetate=4:1). As a result, 1.3 g of a transparent oil-like compound (1 B) was obtained. The yield was 86%. The compound (1 B) was identified by 1 H-NMR. 1H-NMR (400 MHz, CDCl3):δ=1.19-1.82(m,20H,-CH2-), 1.90(m,2H,-CH2-), 2.13(m,2H,-CH2-), 2.45(m,1H,Ar-CH), 3.25(m,1H,O-CH-)3.49(t,2H,-O-CH2-), 3.93(t,2H,-O-CH2-), 4.10-4.20(m,4H,-O-CH2-), 5.79-5.82(d,2H,acryl), 6.08-6.16(dd,2H,acryl), 6.37-6.44(d,2H,acryl), 6.82(d,2H, aromatic H), 7.10(d,2H, aromatic H)
82%	With toluene-4-sulfonic acid In dichloromethane at 0 - 20℃; for 1.5h; Inert atmosphere;
82%	With toluene-4-sulfonic acid In dichloromethane at 0 - 20℃; for 1.5h;	8 Preparation of 2-(6-bromohexyloxy)tetrahydro-2H-pyran (23) 6-bromohexan-1-ol (22) (7.25 ml, 55.2 mmol) was brought up in DCM (55 mL) and cooled to 0° C. To this solution was added tosylic acid (0.095 g, 0.55 mmol), then dihydropyran (6.31 ml, 69.0 mmol) was added drop wise. Upon completion of addition, the reaction was stirred for 1.5 hours allowing it to warm to ambient temperature. TLC showed complete conversion to protected alcohol. The mixture was diluted with ether (300 mL), and washed with sat NaHCO3. The organic layer was dried over MgSO4 and concentrated in vacuo. The crude product was purified by column chromatography (100% DCM) to give the product as a clear colorless oil (12.05 g, 82%). Rf=0.74 (2:1 hexanes to EtOAc); 1H NMR [400 MHz, CDCl3] δ 4.55 (dd, 1H, J=4.3 Hz), 3.84 (m, 1H), 3.71 (dt, 1H, J=9.4, 7.0 Hz), 3.47 (m, 1H), 3.38 (t, 2H, J=7.1 Hz), 3.36 (dt, 1H, J=9.4, 7.0 Hz), 1.85 (q, 2H, J=7.2 Hz), 1.80-1.30 (m, 12H); 13C NMR [100 MHz, CDCl3] δ 99.2, 99.0, 67.6, 62.6, 34.1, 32.9, 31.0, 29.8, 28.2, 25.7, 19.9 ppm; HRMS [ESI] m/z 271.00278 (calc'd for C11H21BrO2+Li: 271.08795); Elem. Anal. C, 50.17; H, 8.00; Br, 29.80 (calc'd for C11H21BrO2: C, 49.82; H, 7.98; Br, 30.13).
81%	With DL-10-camphorsulphonic acid In dichloromethane for 0.5h;
81%	With toluene-4-sulfonic acid In dichloromethane at 0 - 20℃; Inert atmosphere;
81%	With toluene-4-sulfonic acid In dichloromethane at 0 - 20℃; for 12h; Inert atmosphere;	1 2-(6-Bromohexyloxy)tetrahydro-2H-pyran 11, was first synthesized according to the following reaction scheme. In particular, a cooled, flame-dried round bottom flask equipped with a stir bar and septum was charged, under argon and at 0° C., with 6-bromo-1-hexanol 10 (7.6551 g, 42.28 mmol, 1 eq), dry DCM (10 ml), dihydropyran (4.25 ml, 46.51 mmol, 1.1 eq), and p-toluenesulfonic acid (0.4030 g, 2.12 mmol, 5 mol %). The reaction was allowed to stir at room temperature overnight, and was quenched by diluting with water (50 ml) and DCM (50 ml) in a separatory funnel. The organic layer was washed three times with brine (3×50 ml), dried (MgSO4), filtered, and evaporated to dryness under reduced pressure. Flash chromatography (SiO2: 15:1 hexanes to ethyl acetate) gave 11 (9.0902 g, 81% yield) as a clear oil. 1H NMR (500 MHz, CDCl3): δ 84.56 (t, J=2.75 Hz, 1H), 3.85 (m, 1H), 3.72 (m, 1H), 3.51 (m, 1H), 3.40 (m, 3H), 1.95-1.36 (br m, 14H). 13C NMR (126 MHz, CDCl3): δ 99.05, 67.56, 62.54, 34.02, 32.92, 30.94, 29.73, 28.18, 25.67, 25.65, 19.87. HRMS-FAB (m/z): [M+H] calcd for C11H22O2Br, 265.0803; found 265.0804.
75%	With hydrogenchloride for 5h; Ambient temperature;
71%	With toluene-4-sulfonic acid In toluene at 100℃; Inert atmosphere;
70%	With hydrogen cation
66%	In dichloromethane
61%	With pyridinium 4-toluenesulfonate In dichloromethane Cooling with ice;	5 5.3.5. 2-((6-Bromohexyl)oxy)tetrahydro-2H-pyran (7) 1-Bromohexanol (7.0 g, 1 eq.) was dissolved in CH2Cl2 and cooled with an ice bath, then dihydropyran (5.3 ml, 1.5 eq.) and pyridinium p-toluenesulfonate (50 mg, 0.05 eq.) were added. After stirring overnight, the mixture was washed with H2O (×2), once with brine, dried with Na2SO4, filtered, and the solvent was removed under reduced pressure. The resulting solid was dissolved in hexane:Et2O (5 mL, 20:1), loaded onto a silica column, and eluted using hexane:Et2O (20:1). Product containing fractions were combined and the solvent removed to afford compound 7 (6.442 g, 61% yield).
60%	With trichlorophosphate
	With DL-10-camphorsulphonic acid In dichloromethane
	With toluene-4-sulfonic acid
	With hydrogen cation
	With pyridinium 4-toluenesulfonate In dichloromethane for 5h;
	With toluene-4-sulfonic acid In chloroform
	With trichlorophosphate In tetrahydrofuran
	With hydrogenchloride at 20℃; for 16h;
	With pyridinium 4-toluenesulfonate In dichloromethane at 20℃; for 5h; Cooling with ice bath;
	With pyridinium 4-toluenesulfonate In dichloromethane at 20℃;
	Stage #1: 1-bromo-6-hexanol With toluene-4-sulfonic acid In dichloromethane at 0℃; for 0.166667h; Stage #2: 3,4-dihydro-2<i>H</i>-pyran In dichloromethane at 0℃; for 3h;	21 THP-protected 6-bromo-1-hexanol: [0317j THP-protected 6-bromo-1-hexanol: Into an oven-dried 50 mL round-bottomflask, 6-Bromo-1-hexanol (1 mmol) and p-toluenesulfonic acid monohydrate (catalyticamount) are dissolved in 20 mL of dichloromethane. The mixture was allowed to mix at 0°C for 10 mm. With stirring, 3,4-Dihydro-2H-pyran (3 mmol) dissolved in 10 mL of dichloromethane was then dropwise added to the reaction mixture at 0°C. The progress of the reaction was monitored by TLC and the reaction was observed to be completed within 3hours. The reaction mixture was concentrated under reduced pressure and the resulting residue was purified by silica gel chromatography. Fractions contain the desired product were pulled and the solvent was removed under reduced pressure to afford the desired product.
	With pyridinium 4-toluenesulfonate In dichloromethane at 20℃;

Yield	Reaction Conditions	Operation in experiment
92%	With potassium carbonate In acetone for 24h; Heating;
92%	With potassium carbonate; potassium iodide In butanone
91%	With potassium carbonate In acetone at 64℃; for 24h;	1 5.0 g (25.6 mmol) of 4-cyano-4'-hydroxybiphenol, 4.6 g (25.6 mmol) of 6-bromo-1-hexanol, 7.0 g (50 mmol) of potassium carbonate and 50 ml of acetone were added to a 100 ml round bottom flask equipped with a condenser to provide a mixture, followed by reaction at 64°C for 24 hours under stirring. After completion of the reaction, the solvent was distilled off under reduced pressure to obtain a yellow wet solid. Thereafter, this solid was mixed with 70 ml of water, to which 50 ml of diethyl ether was added for extraction. The extraction was repeated three times. Anhydrous magnesium sulfate was added to a separated organic phase for drying and after filtration, the solvent was distilled off under reduced pressure to obtain a yellow solid. This solid was dissolved in 3 ml of ethyl acetate and purified by silica gel column chromatography (column: silica gel 60, 0.063-0.200 mm, made by Merck & Co., eluate: hexane/ethyl acetate = 1/1). The solvent was distilled off from the resulting solution to obtain 6.9 g of a white solid. The solid was subjected to measurement of NMR with the results shown below. From the results, it was confirmed that the white solid was made of an intermediate compound (A1) shown in the following synthetic scheme (yield: 91%). 1H-NMR(DMSO-d6) δ: 1.26(m, 6H), 1.69(m, 2H), 3.37(t, 2H), 4.03(t, 2H), 7.06(d, 2H), 7.69(d, 2H), 7.85(m, 4H).

91%	With potassium carbonate In acetone at 64℃; for 24h;	1 [Synthesis Example 1]; Synthesis of polymerizable liquid crystal compound (E3); In a 100-mL pear-shaped flask fitted with a condenser, 4-cyano-4'-hydroxybiphenol (5.0 g, 25.6 mmol), 6-bromo-1-hexanol (4.6 g, 25.6 mmol), potassium carbonate (7.0 g, 50 mmol) and acetone (50 mL) were placed and combined into a mixture. The mixture was subjected to a reaction at 64°C for 24 hours under stirring. After completion of the reaction, the solvent was distilled off under reduced pressure to obtain yellow wet solid. Subsequently, the solid and water (70 mL) were mixed. Diethyl ether (50 mL) was added, followed by extraction. The extraction was conducted three times. An organic layer was separated, to which anhydrous magnesium sulfate was added to dry the same. Subsequent to filtration, the solvent was distilled off under reduced pressure to obtain yellow solid. The solid was dissolved in ethyl acetate (3 mL), followed by purification by silica gel column chromatography (column: "Silica Gel 60," 0.063-0.200 mm, product of Merck & Co., Inc., eluent: hexane/ethyl acetate = 1/1). From the thus-obtained solution, the solvent was distilled off to obtain white solid (6.9 g). The results of a measurement of the solid by NMR are shown below. From the results, the white solid was confirmed to be an intermediate compound (A1) represented by the below-described synthesis scheme (yield: 91%). 1H-NMR(DMSO-d6) δ: 1.26(m,6H), 1.69(m,2H), 3.37(t,2H), 4.03(t,2H), 7.06(d,2H), 7.69(d,2H), 7.85(m,4H).
91%	With potassium carbonate; potassium iodide In butanone at 80℃; for 48h; Inert atmosphere;
91%	With potassium carbonate In acetone at 64℃; for 24h;	2.A2 Synthetic Example 2 Synthesis of polymerizable liquid crystal compound (E2) [Show Image] 5.0 g (25.6 mmol) of 4-cyano-4'-hydroxybiphenyl, 4.6 g (25.6 mmol) of 6-bromo-1-hexanol, 7.0 g (50 mmol) of potassium carbonate and 50 ml of acetone were added to a 100-ml round-bottomed flask equipped with a condenser tube to provide a mixture, followed by reaction under agitation at 64°C for 24 hours. After completion of the reaction, the solvent was distilled off under reduced pressure to obtain a yellow wet solid. Thereafter, this solid and 70 ml of water were mixed together, to which 50 ml of diethyl ether was added for extraction. The extraction was repeated three times. The separated organic phase was dried by addition of anhydrous magnesium sulfate and filtered, followed by distilling off the solvent under reduced pressure to obtain a yellow solid. This solid was dissolved in 3 ml of ethyl acetate and purified according to silica gel column chromatography (column: silica gel 60, 0.063 to 0.200 mm, made by Merck KGaA, eluate: hexane/ethyl acetate = 1/1). The solvent was distilled off from the solution to obtain 6.9 g of a white solid. The results of NMR measurement of the solid are indicated below. From the results, it was confirmed that this white solid was an intermediate compound (A2) (yield: 91%) 1H-NMR (DMSO-d6) δ:1.26 (m, 6H), 1.69 (m, 2H), 3.37 (t, 2H), 4.03 (t, 2H), 7.06 (d, 2H), 7.69 (d, 2H), 7.85 (m, 4H).
91%	With potassium carbonate In acetone at 64℃; for 24h;	2 n a 100 ml eggplant flask equipped with a cooling tube,5.0 g (25.6 mmol) of 4-cyano-4'-hydroxybiphenol,4.6 g (25.6 mmol) of 6-bromo-1-hexanol,7.0 g (50 mmol) of potassium carbonate,And 50 ml of acetone were added to the mixture,The reaction was carried out with stirring at 64 DEG C for 24 hours.After completion of the reaction, the solvent was distilled off under reduced pressure to obtain a wet solid of yellow color. Thereafter, this solidAnd water (70 ml) were mixed and extracted with 50 ml of diethyl ether. Extraction was carried out three times.The organic layer separated was dried over anhydrous magnesium sulfate,After filtration, the solvent was distilled off under reduced pressure to obtain a yellow solid.This solid was dissolved in 3 ml of ethyl acetate,Silica gel column chromatography (column: silica gel 60,0.063-0.200 mm,Eluent: hexane / ethyl acetate = 1/1).The solvent was distilled off from the obtained solution,6.9 g of a white solid was obtained.The result of measurement of this solid by NMR is shown below.From this result, it was confirmed that the white solid was the intermediate compound (A2) (yield: 91%).
75%	With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 3.5h; Cooling with ice; Inert atmosphere;
68%	With potassium carbonate In acetone for 24h; Reflux; Inert atmosphere;
	With potassium carbonate In N,N-dimethyl-formamide Heating; Yield given;
	With potassium carbonate In ethanol for 24h; Heating;
	With potassium carbonate In N,N-dimethyl-formamide at 100℃; for 4h;
	With potassium carbonate In butanone Heating;
	With potassium carbonate In acetone Heating;
	With potassium carbonate; potassium iodide In butanone

Yield	Reaction Conditions	Operation in experiment
95%	With oxalyl dichloride; dimethyl sulfoxide In dichloromethane at -70 - -20℃; for 4h;
93%	With pyridinium chlorochromate In dichloromethane	EXAMPLES; 6-BROMOHEXANAL [1] Ref : LIEBIGS. Ann. Chem. , 1991,569 In a round bottomed flask fitted with a reflux condenser, 8.63 g (40.02 mmol) of pyridinium chlorochromate (PCC) was suspended in DCM (60ML) and the mixture brought to reflux. At this point a solution of 6-bromohexanol (4. 31G, 26.68 mmol) in DCM (5ML) was added in one portion to the stirred suspension. After 1. 5H, 50 ml of diethyl ether was added and the supernant liquid decanted from the black gum. The insoluble residue was washed several times with diethyl ether. The combined organic washings was passed through a pad of silica gel, eluting with DCM and concentrated to give a light green oil (93%). To minimise decomposition, the crude aldehyde was used in the next step without purification.
88%	With Burgess Reagent; dimethyl sulfoxide at 20℃; for 0.0833333h; Schlenk technique; Inert atmosphere;

87%	With anhydrous Sodium acetate; pyridinium chlorochromate In dichloromethane
85%	With magnesium(II) sulfate; pyridinium chlorochromate In dichloromethane for 1.5h; Ambient temperature;
80%	With pyridinium chlorochromate In tetrahydrofuran at 20℃; for 1h;
79%	With pyridinium chlorochromate In dichloromethane at 0℃; for 3h;
76%	With oxalyl dichloride; dimethyl sulfoxide; triethylamine In dichloromethane at -78 - 20℃;
74%	With pyridinium chlorochromate In dichloromethane at 0℃; for 14.5h;	1 Starting with 6-bromohexanol, oxidation to the corresponding aldehyde was performed employing a modified procedure of Hon et al., Tetrahedron 1998, 54, 5233. Under a positive pressure of nitrogen, 3.57 g of pyridinium chlorochromate (16.6 mmol) were combined with 25 mL of freshly distilled CH2Cl2 in a 50 mL round bottomed flask and allowed to cool at 0° C. for 30 min prior to the addition of 6-bromo-hexan-1-ol (2.00 g, 11.0 mmol). The solution was allowed to stir at 0° C. for 14 hr and then gradually warmed to rt. The solution mixture was concentrated on the rotary evaporator and then diluted with 50 mL of Et2O and passed through a pad of CELITE. The solution that passed was combined with 3 subsequent ether washes (15 mL) and concentrated to form a clear liquid. Traces of residual solvent were removed under vacuum for 2 hr. Product was obtained (1.46 g, 74% yield), in significant purity to be used in subsequent reactions without additional purification. 1H NMR: 9.74 (s, 1H), 3.38 (t, J=7, 2H), 2.45 (t, J=6, 2H), 1.87-1.80 (m, 2H), 1.65-1.58 (m, 2H), 1.49-1.42 δ (m, 2H); 13C NMR: 202.2, 64.2, 43.6, 32.4, 27.6. 21.9 δ. Spectroscopic data correlated with that previously reported.
70%	With pyridinium chlorochromate In dichloromethane at 20℃;
69%	With anhydrous Sodium acetate; pyridinium chlorochromate In dichloromethane for 1.5h; Ambient temperature;
57%	With pyridinium chlorochromate In dichloromethane at 20℃; for 24h;
56%	With pyridinium chlorochromate In dichloromethane at 20℃; for 2h; Inert atmosphere;
55%	With pyridinium chlorochromate In dichloromethane at 20℃; for 16h;
52%	With pyridinium chlorochromate In dichloromethane at 20℃; for 16h;
45%	With pyridinium chlorochromate In dichloromethane at 20℃; for 3h; Inert atmosphere;
	With aluminum(III) oxide; pyridinium chlorochromate In dichloromethane at 20℃; for 0.5h;
	With oxalyl dichloride; dimethyl sulfoxide; triethylamine In dichloromethane at -78 - 20℃;
	With pyridinium chlorochromate In dichloromethane at 20℃; for 3h;
	With pyridinium chlorochromate
	Stage #1: 1-bromo-6-hexanol With oxalyl dichloride; dimethyl sulfoxide In dichloromethane; toluene at -78℃; Inert atmosphere; Stage #2: With triethylamine In dichloromethane; toluene at -78 - 20℃; Inert atmosphere;
	With oxalyl dichloride; dimethyl sulfoxide In dichloromethane at -78 - 78℃; for 1h;	(E)-methyl 8-bromooct-2-enoate (5b) A solution of oxalyl chloride (2.70 mL, 30.9 mmol) in DCM (70 mL) was cooled to -78 °C and a solution of anhydrous DMSO (2.80 mL, 39.2 mmol) in DCM (70 mL) was added dropwise. After 10 minutes a solution of 6-bromohexan-1-ol (4b) (2.02 mL, 15.4 mmol) in DCM (28 mL) was added dropwise and stirred at 78 °C. After 1 hour the reaction mixture was allowed to warm up to room temperature concurrent with the slow addition of triethylamine (14.0 mL). The previously prepared phosphorane (8.52 g, 25.5 mmol) was added to the reaction mixture, the flask was purged with argon and the stirred overnight at room temperature. It was washed with 0.1 M HCl (2×50 mL), cc. NaHCO3 (50 mL), dist. water (50 mL) and brine (50 mL), the organic phase was dried over MgSO4. Purification by column chromatography (hexane/EtOAc : 9/1) gave 5b (2.78 g, 78%) as pale yellow oil.
	With pyridinium chlorochromate In dichloromethane at 20℃; for 2h;
	With oxalyl dichloride; dimethyl sulfoxide; triethylamine at -60℃;
	With pyridinium chlorochromate In dichloromethane at 20℃; for 18h;	Preparation of 9-Bromononanal General procedure: Pyridinium chlorochromate (38.7 g, 180 mmol) and silica 60A (39 g, particle size 35-70 micron) suspended in DCM (250 mL) were stirred at RT for 45 minutes. 9-Bromononanol (26.7 g, 120 mmol) was added, in one portion, and the suspension was stirred at RT for 18 hours. The reaction mixture was filtered through a celite plug and the resulting filtrate concentrated under vacuum affording the title compound (28.0 g, >100%). The material was used without further purification in the next step.
	Stage #1: 1-bromo-6-hexanol With oxalyl dichloride; dimethyl sulfoxide In dichloromethane at -78℃; for 1.5h; Stage #2: With triethylamine In dichloromethane at -78 - 20℃; for 1h;	42.1 Step 1: Preparation of compound 150-2 To a solution of (COCl) 2 (6.7 mL, 77.0 mmol, 2.0 eq) in 30 mL of DCM, DMSO (10.9 mL, 154 mmol, 4.0 eq) was added at -78 . After stirring for 20 min, 6-bromohexan-1-ol (6.8 g, 37.6 mmol, 1.0 eq) was added. After stirring for another 1.5 h at -78 , Et 3N (10 mL) was added and the reaction mixture was stirred at room temperature for 1.0 h. The reaction mixture was diluted with CH 2Cl 2 (100 mL) and washed water (50 mL) and brine (500 mL) . The combined organic layers were dried over Na 2SO 4 and solvents were removed in vacuo. Evaporation of the solvent gave the crude product which was purified by column (silica gel, 0-5%EA in PE) chromatography and the pure product fractions were evaporated to provide the product 150-2 (7.0 g, crude) as a colorless oil. 1H NMR (400 MHz, CDCl 3) δ: 1.45-1.51 (m, 2H) , 1.53-1.70 (m, 2H) , 1.85-1.91 (m, 2H) , 2.44-2.50 (m, 2H) , 3.40-3.43 (m, 2H) , 9.78 (s, 1H) .

Yield	Reaction Conditions	Operation in experiment
100%	With silver nitrate In acetonitrile Heating;
92%	With silver nitrate In acetonitrile for 24h; Ambient temperature;
92%	With silver nitrate In acetonitrile for 2h; Heating / reflux;	1.1a 6-Bromohexan-1-ol (10 g, 55.2 mmol) was dissolved in acetonitrile (200 mL). To this solution was added silver nitrate (12.19 g, 71.76 mmol, 1.3 equivalents) and the reaction mixture was refluxed under nitrogen atmosphere for 2 hours. After removal of the solid by filtration, the solvent was evaporated under reduced pressure. The residue was extracted with ethyl acetate, then washed with water, brine, dried over sodium sulfate, filtered through a small pad of silica gel and then evaporated under reduced pressure to give the title compound as a pale yellow oil (8.28 g, 92% yield). 1H NMR (400 MHz, CDCI3) δ 4.47 (t, J=6.7 Hz, 2H), 3.67 (t, J=6.5 Hz, 2H), 2.04 (s, 1H), 1.82-1.73 (m, 2H), 1.65-1.57 (m, 2H), 1.52-1.40 (m, 4H).

90%	With silver nitrate In acetonitrile for 8h; Reflux; Inert atmosphere;	6-(Nitrooxy)hexan-1-ol, 8⁹ Silver nitrate (698 mg, 4.11 mmol) was added to a solution of 6-bromohexan-1-ol 14 (500 mg, 2.76 mmol) in CH3CN (15 mL) and stirred for 8 h under reflux. The mixture was poured onto brine (20 mL), and the precipitate was filtered. The filtrate was extracted with diethyl ether (5 × 20 mL), and dried over MgSO4, filtered and the solvent was removed under reduced pressure to yield 6-(nitrooxy)hexan-1-ol 8 (405 mg, 2.48 mmol, 90%) as a clear pale yellow oil, which was used without any further purification: Rf 0.29 (30:70 EtOAc:PE, KMnO4); 1H NMR (400 MHz; CDCl3) δ 4.45 (2H, t, J 6.7 Hz, CH2-6), 3.65 (2H, t, J 6.5 Hz, CH2-1), 1.70-1.78 (2H, m, CH2-5), 1.54-1.62 (2H, m, CH2-2), 1.38-1.48 (5H, m, 2 × CH2-3, 4, OH); 13C NMR (100 MHz;CDCl3) δ 73.4 (CH2, C-6), 62.6 (CH2, C-1), 32.5 (CH2, C-2), 26.8 (CH2, C-5), 25.6, 25.4 (CH2 × 2, C-3, 4); m/z (ES+) 164 ([M+H]+, 100%). The data were in agreement with the literature values.9
86%	With silver nitrate In acetonitrile at 20℃; for 72h;	5.1 6-Nitrooxy-hexan-l-olTo a solution of 6-bromohexan-l-ol (2.2 mL, 16.6 mmol) in CH3CN(100 mL) was added silver nitrate (5.95 g, 35 mmol, 2 eq) . The reaction was stirred at room temperature for 3 days. The reaction was quenched by addition of a solution of brine.After 15 min of stirring, the solution was filtered, extracted with ethyl acetate, washed with H2O, brine, dried over sodium sulfate, filtered and evaporated. The residue was purified by column chromatography (Biotage System, SNAP Cartridge silica 100 g, eluent: n-hexane/ethyl acetate 80/20 to n-hexane/ethyl acetate 50/50 during 12 CV) to give the desired product as a colorless oil (2.34 g, 86%).1H NMR (300 MHz, CDCl3) . 4.47 (t, J = 6.6 Hz, 2H), 3.68 (t, J = 6.1 Hz, 2H), 1.77 (m, 2H), 1.62 (m, 2H), 1.48 (m, 4H), 1.27 (s, IH) .
86%	With silver nitrate In acetonitrile at 20℃; for 72h;	2.1 Synthesis of 6-Nitrooxy-hexan-l-ol Example 2 Synthesis of 6-(nitrooxy)hexyl 3-methyl-3-(2,4,5-trimethyl-3,6-dioxocyclohexa- 1 ,4-dienyl)butanoate (Compound 2) Step 1 : Synthesis of 6-Nitrooxy-hexan-l-ol ,ONCL A solution of 6-bromohexan-l-ol (2.2 mL, 16.6 mmol) in CH3CN (100 mL) was added with silver nitrate (5.95 g, 35 mmol, 2 eq). The reaction was stirred at room temperature for 3 days. The reaction was quenched by addition of a solution of brine. After 15 min of stirring, the solution was filtered, extracted with ethyl acetate, washed with H20, brine, dried over sodium sulfate, filtered and evaporated. The residue was purified by column chromatography (Biotage System, SNAP Cartridge silica 100 g, eluent: n-hexane/ethyl acetate 80/20 to n-hexane/ethyl acetate 50/50 during 12 CV) to give the desired product as a colorless oil (2.34 g, Yield:86%). 1H NMR (300 MHz, CDC13) 4.47 (t, J = 6.6 Hz, 2H), 3.68 (t, J = 6.1 Hz, 2H), 1.77 (m, 2H), 1.62 (m, 2H), 1.48 (m, 4H), 1.27 (s, 1H).
86%	With silver nitrate In acetonitrile at 20℃; for 72h;	2.1 Synthesis of 6-Nitrooxy-hexan-l-ol Example 2 Synthesis of 6-(nitrooxy)hexyl 3-methyl-3-(2,4,5-trimethyl-3,6-dioxocyclohexa- 1 ,4-dienyl)butanoate (Compound 2) Step 1 : Synthesis of 6-Nitrooxy-hexan-l-ol ,ONCL A solution of 6-bromohexan-l-ol (2.2 mL, 16.6 mmol) in CH3CN (100 mL) was added with silver nitrate (5.95 g, 35 mmol, 2 eq). The reaction was stirred at room temperature for 3 days. The reaction was quenched by addition of a solution of brine. After 15 min of stirring, the solution was filtered, extracted with ethyl acetate, washed with H20, brine, dried over sodium sulfate, filtered and evaporated. The residue was purified by column chromatography (Biotage System, SNAP Cartridge silica 100 g, eluent: n-hexane/ethyl acetate 80/20 to n-hexane/ethyl acetate 50/50 during 12 CV) to give the desired product as a colorless oil (2.34 g, Yield:86%). 1H NMR (300 MHz, CDC13) 4.47 (t, J = 6.6 Hz, 2H), 3.68 (t, J = 6.1 Hz, 2H), 1.77 (m, 2H), 1.62 (m, 2H), 1.48 (m, 4H), 1.27 (s, 1H).
86%	With silver nitrate In acetonitrile at 20℃; for 72h;	2.1 Synthesis of 6-Nitrooxy-hexan-l-ol A solution of 6-bromohexan-l-ol (2.2 mL, 16.6 mmol) in CH3CN (100 mL) was added with silver nitrate (5.95 g, 35 mmol, 2 eq). The reaction was stirred at room temperature for 3 days. The reaction was quenched by addition of a solution of brine. After 15 min of stirring, the solution was filtered, extracted with ethyl acetate, washed with H20, brine, dried over sodium sulfate, filtered and evaporated. The residue was purified by column chromatography (Biotage System, SNAP Cartridge silica 100 g, eluent: n-hexane/ethyl acetate 80/20 to n-hexane/ethyl acetate 50/50 during 12 CV) to give the desired product as a colorless oil (2.34 g, Yield: 86%). 1H NMR (300 MHz, CDC13) 4.47 (t, J= 6.6 Hz, 2H), 3.68 (t, J= 6.1 Hz, 2H), 1.77 (m, 2H), 1.62 (m, 2H), 1.48 (m, 4H), 1.27 (s, 1H).

Yield	Reaction Conditions	Operation in experiment
100%	With Caswell No_. 744A In N,N-dimethyl-formamide
99%	With Caswell No_. 744A In lithium hydroxide monohydrate; N,N-dimethyl-formamide	2.2 (2) (2) Synthesis of 6-azido-1-hexanol 6-Bromo-1-hexanol (5.00 g, 27.6 mmol) was dissolved in 12 mL of DMF. To this solution, sodium azide (4.00 g, 61.5 mmol) was added and the mixture was stirred at 50° C. for 3 days. The mixture was concentrated by evaporation, and distilled water (10 mL) was added thereto. This aqueous solution was extracted six times with diethyl ether, and the combined organic extracts were dried over magnesium sulfate, followed by evaporation to give a product (6-azido-1-hexanol). The yield was 99% or more. 1H NMR (CDCl3): δ1.4-1.8 (9H, N3CH2(CH2)4CH2OH), δ3.3 (2H, N3CH2(CH2)4CH2OH), δ3.7 (2H, N3CH2(CH2)4CH2OH).
98%	With Caswell No_. 744A In N,N-dimethyl-formamide at 80℃; for 16h;

Yield	Reaction Conditions	Operation in experiment
98%	With 1H-imidazole; In DMF (N,N-dimethyl-formamide); at 0℃; for 3.75h;	Add a solution of tert-butyldimethylsilyl chloride (5.0 g, 33.1 mmol) in dimethylforamide (DMF) (70 mL) dropwise over 15 minutes to a solution of 6- bromohexanol (5.0 g, 27.6 mmol) and imidazole (4.7 g, 69 mmol) in DMF (80 mL) at 0C under nitrogen protection and stir the mixture for another 3.5 hours. Dilute the mixture with water (400 mL) and extract with diethyl ether (3 x 150 mL). Dry the combined organic extracts over sodium sulfate and remove the solvent under reduced pressure. Purify the crude product by flash column chromatography on silica gel, eluting with ethyl acetate/hexanes (1: 19), to provide (6-bromohexyloxy)-tert-butyldimethylsilane (8.05 g, 98%).
98%	With dmap; triethylamine; In dichloromethane; at 20℃; for 6h;Product distribution / selectivity;	6-Bromo-1-tert-butyldimethylsilyloxy hexane (Compound 61, Scheme 21) was prepared by adding TBSCl (2 grams, 13.26 mmol) to a stirred solution of Compound 60 (6-bromohexanol, 2 grams, 11.05 mmol), triethylamine (2.3 ml, 16.57 mmol) and DMAP (11 mg, 1.1 mmol) in dry CH2Cl2 (15 ml). The reaction mixture was stirred for 6 hours at room temperature, and upon completion of the reaction as indicated by TLC, the reaction mixture was quenched with aqueous NH4Cl, extracted with CH2Cl2, the combined organic layer was washed with water and dried over MgSO4, and the solvents were removed under reduced pressure. The residue was purified by column chromatography using silica gel and hexane/ethyl acetate (100:5) as eluent to afford Compound 61 in the form of a colorless oil (3.2 grams, 98% yield).1H NMR (500 MHz, CDCl3)-δ: 3.603 (t, J=6.5 Hz, 2H), 3.404 (t, J=7 Hz, 2H), 1.90-1.83 (m, 2H), 1.57-1.46 (m, 2H), 1.44-1.41 (m, 2H), 1.38-1.34 (m, 2H), 0.89 (s, 9H), 0.04 (s, 6H);13C NMR (125 MHz, CDCl3)-δ: 63, 33.9, 32.8, 32.6, 28, 26, 25, 18.3, -5.3;MS (ESI), m/z: 295 (MH+).
95%	With dmap; triethylamine; In dichloromethane; at 20℃; for 5h;	General method: To a stirred solution of 11 (2.00 g, 1 equiv) in dry CH2Cl2 (30 mL), TBSCl (1.3 equiv), DMAP (0.05 equiv) and Et3N (1.3 equiv) was added. The reaction solution was stirred atroom temperature for 5 h, and then a saturated solution of NH4Cl was added. The mixture was extracted with CH2Cl2. The organic layer was dried with MgSO4 and concentrated. The residue was subjected to silica gel chromatography with petroleum ether/EtOAc (100:1) to give 12.

95%	With dmap; N,N-diphenylaminobenzene; In dichloromethane; at 20℃;Inert atmosphere;	To a solution of 6,bromo-n-hexanol (4 g ; 22 mmol ; 1 eq.) into dry DCM (50 mL) under inert atmosphere was added tert-Butyldimethylsilyl chloride (3.35 g ; 29 mmol ; 1.3 eq.), Triethylamine (4 mL ; 29 mmol ; 1.3 eq.) and 4-(Dimethylamino)pyridine (130 mg ; 1.1 mmol ; 0.05 eq.). The reaction mixture was stirred overnight at RT. A saturated solution of ammonium chloride (100 mL) was then added to the mixture and extracted with DCM (2x100 mL). The combined organic layers were washed with water, dried over MgSO4, filtered and evaporated under vacuum. The obtained residue was purified over a silica gel column EP : EtOAc (95 : 5) and led to 6.2 g of a colorless oil (21 mmol ; 95% yield). 1H NMR (400 MHz ; CDCl3): δ 3.56 (t, 2H, J 6.4 Hz), 3.36 (t, 2H, J 6.8 Hz), 1.82 (quint, 2H, J 7.3 Hz), 1.46 (m, 2H), 1.33 (m, 4H), 0.85 (s, 9H), 0 (s, 6H). 13C NMR (101 MHz ; CDCl3): δ 63, 33.9, 32.8, 32.6, 28, 26, 25, 18.4, -5.27 ; 3 signals obscured or overlapping. ESI MS : 297.1 m/z : [M+H]+ ; 319.1 m/z : [M+Na]+
92.4%	With 1H-imidazole; In tetrahydrofuran; at 0℃;	6-Bromo-1-hexanol(20 g, 110.42 mmol) was dissolved in dry tetrahydrofuran(700 ml) and cooled to 0 C. under argon atmosphere, to which were added imidazole(15 g, 220.84 mmol) and t-butyldimethylsilyl chloride(33 g, 220.84 mmol) and the resulting solution was stirred overnight. After the reaction was completed, the mixture was poured in ice-water and extracted with ethyl acetate. The organic solvent was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. This crude product was purified by column chromatography on silica gel, eluting with ethyl acetate:n-hexane=1:40. After removal of the solvent, 30 g of the title compound was obtained as colorless oil. (yield: 92.4%) [00808] 1H-NMR (300 MHz, CDCl3) δ: 3.61(t, 2H, J=6.4 Hz), 3.41(t, 2H, J=7.2 Hz), 1.87(m, 2H), 1.561.30(m, 6H), 0.89(s, 9H), 0.05(s, 6H)
90%	With 1H-imidazole; In DMF (N,N-dimethyl-formamide); at 0 - 20℃; for 2h;	6-bromohexanol (3 g, 16.6 mMoles) in 33 ml of anhydrous DMF, under argon atmosphere, was treated with imidazole (2.72 g, 40 mMoles) and the resulting homogeneous solution was cooled down to 0 C. then it was treated with TBSCl in 12 ml of DMF. Temperature was then allowed to warn up gradually to the ambient while reaction evolution was monitored by thin layer chromatography (TLC), silica gel (SiO2) using ethylacetate (EtOAc)-hexane (Hex): 1-2 (v/v). After 2 hours at room temperature (rt) no starting material remained, and the reaction mixture was partitioned between water and EtOAc. After decantation, the aqueous layer was extracted with EtOAc thrice, and the combined organic layers were washed twice with H2O, and brine, dried over MgSO4, and concentrated under reduced pressure. The resulting yellowish oil was purified by short path silica gel column chromatography using EtOAc-Hex:1-4 as eluent to afford the desired silylether (4.4 g, 90% yield) as a colorless oil. [00041] Lithium acetylide ethylene diamine complex (0.65 g, 6 mMoles) was added portionwise to anhydrous DMSO under inert atmosphere. The resulting not completely homogeneous dark brown mixture was cooled down to approximately 5 C., temperature at which the bromosilyl ether was introduced dropwise over 5 minutes. The cold bath was removed and reaction evolution was monitored by NMR of a quenched aliquot. After 5 hours at rt (usually an hour is enough) no starting material remained. The content of the flask was poured carefully into an Erlenmeyer flask containing ice. This was extracted with EtOAc thrice, and the combined organic layers were washed three times (3×) with water and once with brine. Brief drying over MgSO4, and removal of the volatiles under reduced pressure gave a yellow oil. Purification by short path silica gel column chromatography, using EtOAc-Hex:1-19, gave 0.88 g (92% yield) of the desired true alkyne as a colorless oil. [00042] A solution of the alkyne (80 mg, 0.33 mMole) in 1 ml of THF was cooled down to -78 C. under Argon, and it was treated with 0.22 ml of a 1.6 molar solution of n-butyl lithium in hexane. This was then warmed up to the ambient temperature for 20 minutes, then brought back to -78 C., temperature at which 0.2 ml of freshly distilled hexamethylphosphoramide (HMPA) was added, followed by monoprotected 17-ketotestosterone (80 mg, 0.24 mMole) as a suspension in 0.5 ml of THF. After an overnight stirring period at room temperature, the reaction was quenched with saturated ammonium chloride, decanted and extracted with EtOAc (3×). The combined organic layers were washed with brine, dried over MgSO4, and concentrated under reduced pressure to give a light brown oily solid. Column chromatography on a short path SiO2 column, using EtOAc-Hex: 1-9 gave the desired alcohol (50 mg, 36% yield) as a colorless oil. [00043] The silylether (50 mg, 0.088 mMole) was diluted in 2 ml of anhydrous THF under argon. The resulting colorless solution was cooled down to 0 C., and it was treated with a one molar solution of tetrabutyl ammonium fluoride (115 microliters, 1.15 mMoles), and the cold bath was removed. After 3 hours at room temperature, no starting material remained. THF was removed under reduced pressure, and the residual brown oil was diluted in minimum chloroform and loaded on a short path SiO2 column and eluted with EtOAc-Hex:1-2 to 1-1. This 34 mg (85% yield) of the alcohol as a colorless oil. [00044] At 0 C., the Diol (34 mg, 0.0745 mMole) in 0.5 ml of methylene chloride, was treated with triethylamine (22.6 mg, 31 microliters, 0.22 mMoles) followed by mesylchloride (12.8 mg, 8 microliters, 0.11 mMoles). After half an hour at this temperature no starting material remained. The reaction mixture was then concentrated to dryness under vacuum, and it was dissolved in 2 ml of anhydrous DMF and then added with an excess (about 5 equivalents) of sodium azide and the resulting suspension was allowed to stir at room temperature for an overnight period. This was then partitioned between EtOAc and H2O. After decantation, the aqueous layer was extracted with EtOAc (3×), then the combined organic layers were washed with water then brine, dried over MgSO4, and concentrated under reduced pressure to leave a colorless oil. The desired azide 23 mg (64% yield for 2 steps) was isolated by short path SiO2 column, using EtOAc-Hex: 1-4 as eluent. [00045] The azido acetal (11 mg, 0.0228 mMole) in 2 ml of methanol was treated with 0.5 ml of 1.0 normal hydrochloric acid, at rt. for 3 hours. pH was made alkaline (7-8) by careful addition of saturated sodium bicarbonate, and methanol was removed under vacuum. The remaining white oily solid was extracted with CHCl3 until TLC indicated no organic material was present in the aqueous phase. The combined organic layers were dried briefly over MgSO4, and evaporated under vacuum to give an oily solid film. This was dissolved in minimum CHCl3, and loaded on a short SiO2 plug and eluted with EtOAc-Hex: 1...
88%	With 1H-imidazole; In N,N-dimethyl-formamide; at 0℃; for 1h;	13.7 gm (75.4 mmol) of 6-bromo-1-hexanol was dissolved in 100 ml DMF to which was added 15.4 gm (226 mmol) imidazole. The solution was cooled to 0 C. and 20 gm (133 mmol) tert-butyl-dimethyl-silyl-chloride was added. After 1 h the solution was added to 500 ml H2O. The cloudy suspension extracted with 200 ml EtOAc and again with 150 ml EtOAc. The combined organic phases were dried over Na2SO4 and the solvent evaporated under reduced pressure to produce a clear oil. The product (14) was purified by flash chromatography on silica gel eluted with hexanes:EtOAc (99:1); 19.3 gm (88%).
80%	With dmap; triethylamine; In dichloromethane;Product distribution / selectivity;	EXAMPLE 8 6-Bromohexyl tert-butyldimethylsilyl ether (3) A mixture of 6-bromo-1-hexanol (2) (15 g, 83 mmol), tert-butyldimethylsilyl chloride (10.8 g, 72 mmol), triethylamine (15.2 g) and trace of 4-dimethylaminopyridine in dichloromethane (150 mL) was stirred overnight to form a white precipitate. The reaction mixture was then washed with water, and the organic layer was concentrated and subjected to flash chromatography on silica gel using dichloromethane 100% as a mobile phase to give 6-bromohexyl tert-butyldimethylsilyl ether (3) (17.0 g, 80%) as a pale yellow oil. 1H-NMR (CDCl3) : 3.61 (t, 2H, CH2OSi, J=6.3 Hz), 3.40 (t, 2H, BrCH2, J=6.8 Hz), 1.85 (m, 2H, CH2), 1.30-1.70 (m, 6H, CH2), 0.89 (s, 9H, SiC(CH3)3), 0.05 (s, 6H, Si(CH3)2). 13C-NMR (CDCl3): 62.9, 33.9, 32.7, 32.4, 28.0, 25.0, 18.4 and -5.3.
80%	With triethylamine; In 1,2-dichloro-ethane; at 4 - 20℃;	6-Bromohexane-1-ol 20.0 g (110.5 mmol)Was dissolved in 150 mL of 1,2-dichloroethane and cooled to 4 C.tert-Butyldimethylchlorosilane (TBSCl) 18.0 g (120 mmol)After adding 19.5 mL (140 mmol) of triethylamine (TEA)Was added dropwise and stirred at room temperature overnight.Distill off the solvent using a rotary evaporator,Add 300 mL of hexane to suspend,A crude product was obtained by removing insolubles by Celite filtration.The crude product is chromatographed on silica gel {eluting solvent;Hexane: ethyl acetate (continuous gradient)} to give ((6-bromohexyl) oxy) (tert-butyl) dimethylsilane26.0 g (88.0 mmol) was obtained as a colorless oil.The yield was 80%.
79%	With 1H-imidazole; In dichloromethane; at 20℃; for 7h;	Under air, 6-bromo-n-hexanol (1.81g, 10mmol), dichloromethane (20mL), imidazole (1.36g, 20mmol) were added to the reaction flask equipped with a stir bar in sequence. After fully dissolved, tert-butyldimethylchlorosilane (2.26g, 15mmol) was slowly added to the system at room temperature, a large amount of white solid precipitated, and the reaction was performed at room temperature for 7h. The reaction was completed by TLC, the reaction was quenched with saturated ammonium chloride solution, the organic phase was extracted with dichloromethane, dried over anhydrous sodium sulfate, concentrated, silica gel column chromatography, the eluent was petroleum ether: ethyl acetate = 100: 1, product It is a yellow liquid 2.33g, the yield is 79%, and the purity of 1H NMR is greater than 98%.
2.6 g	With 1H-imidazole; In dichloromethane;	Imidazole (1.1 g, 16.56 mmol) and TBS-Cl (1.37 g, 9.11 mmol) were added to a stirring solution of 6-bromohexanol (1.5 g, 8.28 mmol) in CH2Cl2 (80 mL). The resulting mixture was stirred over night then quenched with H2O (100 mL). The aqueous layer was extracted with CH2Cl2 (3×50 mL). The combined organic layers were washed with brine, dried over Na2SO4, and concentrated to give the title compound (2.6 g) as clear oil. The compound was used with no further purification.

Yield	Reaction Conditions	Operation in experiment
99%	In acetonitrile for 24h; Reflux;	(6-Hydroxyhexyl)triphenylphosphonium bromide (10) A mixture of 6-bromohexan-1-ol (9) (10.13 g, 5.63 mmol) and triphenylphosphine (16.23 g,6.19 mmol) in anhydrous acetonitrile (30 mL) was heated at reflux for 24 h, and a whiteprecipitate appeared. The reaction mixture was cooled to room temperature and acetonitrilewas decanted. The phosphonium salt obtained was dissolved in chloroform (80 mL) andprecipitated out by treating with Et2O (200 mL). The mixture was stirred at room temperatureovernight and filtered. The yield of 10 was 99% (24.71 g, white solid).
98.8%	In ethanol Heating;
95%	In acetonitrile at 90℃; for 24h;	1.4 (4) Synthesis of 3a With a magnetic stirring device,In a 100 mL round bottom flask with reflux condenser and airway device, triphenylphosphine (1.049 g, 4.0 mmol) and 6-bromo-1-hexanol (0.724 g, 4.0 mmol) were added sequentially, and anhydrous acetonitrile (25 ml) was added. The reaction was heated under reflux at 90 ° C for 24 h under nitrogen atmosphere. After the reaction was completed, the solvent was removed under reduced pressure. Then, a silica gel column was obtained using dichloromethane:methanol (20:1, V/V) as a solvent to afford white solid 3a (1.685 g, 95%).

92%	In acetonitrile for 48h; Reflux; Darkness; Inert atmosphere;
90%	In acetonitrile for 24h; Reflux;
82%	for 0.0833333h; microwave irradiation;
79%	In acetonitrile at 70℃; for 184h;
78%	In acetonitrile at 82℃; for 48h;	1.Y.1; 1.DN.1 Step 1 : (6-Hydroxyhexyl)triphenylphosphonium bromide Step 1 : (6-Hydroxyhexyl)triphenylphosphonium bromide Chemical Formula: C24H28BrOP Molecular Weight: 443.36 [00644] 6-Bromo-l-hexanol (4.89 g, 27 mmol) and triphenylphosphine (7.87 g, 30 mmol) and 50 mL MeCN were combined in a round bottomed flask. The flask was fitted with a condenser and placed in a heating mantel and the reaction was allowed to stir at 82 °C for 48 h. After this time the reaction was allowed to cool to rt and the solution was cannulated into 200 mL Et^O, producing a white precipitate. The solids were allowed to settle and the solvent was decanted off. 20 mL DCM was added to dissolve the solids and then 100 mL Et^O was slowly added to afford a white precipitate. The solvent was then removed in vacuo to afford clean (6- hydroxyhexyl)triphenylphosphonium bromide (9.4 g, 21.2 mmol, for 78% yield). Ti-NMR (300 MHz, CDCI3) δ: ppm 7.80 (m, 15H); 3.80 (m, 2H); 3.65 (m, 2H); 2.23 (m, 2H); 1.68 (m, 4H); 1.52 (m, 4H).
78%	In acetonitrile at 82℃; for 48h;	1.Y.1 Step 1 : (6-Hydroxyhexyl)triphenylphosphonium bromide 6-Bromo-l-hexanol (4.89 g, 27 mmol) and triphenylphosphine (7.87 g, 30 mmol) and 50 mL MeCN were combined in a round bottomed flask. The flask was fitted with a condenser and placed in a heating mantel and the reaction was allowed to stir at 82 °C for 48 h. After this time the reaction was allowed to cool to rt and the solution was cannulated into 200 mL Et20, producing a white precipitate. The solids were allowed to settle and the solvent was decanted off. 20 mL DCM was added to dissolve the solids and then 100 mL Et^O was slowly added to afford a white precipitate. The solvent was then removed in vacuo to afford clean (6- hydroxyhexyl)triphenylphosphonium bromide (9.4 g, 21.2 mmol, for 78% yield).1H NMR (300 MHz, CDCl3) δ: ppm 7.80 (m, 15H); 3.80 (m, 2H); 3.65 (m, 2H); 2.23 (m, 2H); 1.68 (m, 4H); 1.52 (m, 4H).
30%	In toluene for 6h; Reflux;
	In acetonitrile for 30h; Heating;
	In acetonitrile for 4h; Heating;
	In acetonitrile Heating / reflux;
	In acetonitrile for 72h; Heating / reflux;
	In acetonitrile for 48h; Reflux;	9 (6-hydroxyhexyl)triphenylphosphonium bromide (6-hydroxyhexyl)triphenylphosphonium bromide. A mixture of 6-hydroxyhexyl bromide (10.36 g, 0.057 mol) and triphenylphosphine (5 g, 0.019 mol) in 100 ml of acetonitrile was refluxed for 2 days. After removal of the solvent, the residue was washed three times with ether. The solid was purified by silica chromatography using heptane/ethyl acetate and methylene chloride/MeOH as eluent to give viscous pale white material.
1.1 g	In acetonitrile at 90℃;	(6-Hydroxyhexyl)-triphenyl phosphonium bromide (8) 6-Bromo-1-hexanol (500 mg) and triphenylphosphine (800 mg) in MeCN (4 mL) were refluxed at 90 °C overnight. The reaction mixture was cooled to room temperature and concentrated. The resulting residue was dissolved in acetone and diluted with dry diethyl ether to precipitate the phosphonium salt. Afterstirring for 1 h, the supernatant was obtained by decantation anddried in vacuo to afford the desired phosphonium salt (8, 1.1 g) as white solids: [α]D24 -0.65 (c 0.97, CHCl3); 1H NMR (600 MHz, CDCl3) δ 1.43-1.77 (m, 8H), 2.03 (br s, 1H), 3.54-3.70 (m, 4H), 7.65-7.79 (m, 15H); 13C NMR (200 MHz, CDCl3) δ 22.0 (d, J=4.3 Hz), 22.2 (d, J=49.9 Hz), 24.5, 29.3 (d, J=15.9 Hz), 31.7, 61.0, 118.0 (d, J=86.0 Hz), 130.3 (d, J=12.3 Hz), 133.3 (d, J=10.1 Hz), 134.8 (d, J=2.2 Hz); HRFABMS calcd for C24H29OP [M+-Br] 363.1872, found: 363.1869.
	In acetonitrile
	In acetonitrile at 90℃; Inert atmosphere;
0.95 mmol	In acetonitrile for 48h; Reflux; Inert atmosphere;	Synthesis of (6-hydroxyhexyl)triphenylphosphonium bromide(TPP) To a stirred solution of 6-bromohexan-1-ol (5.0 g, 27.61 mmol) in 70 ml of acetonitrile at room temperature was added triphenylphosphine (7.967 g, 30.37 mmol), and the reaction mixture was heated under reflux for 48 h under a nitrogen atmosphere. Completion of the reaction was confirmed by thin layer chromatography (TLC). The solvent was evaporated under reduced pressure, the crude product was washed with ethanol (2 × 30 ml), and the solid was dried under high vacuum without further purification to afford the title compound (0.95 mmol) as a white solid. The product was confirmed by 1H NMR and liquid chromatography coupled to mass spectrometry (LC-MS). 1H NMR (400 MHz, CDCl3) δ 7.92-7.75 (m, 9H), 7.71 (td, J = 7.5, 3.4 Hz, 6H), 3.87-3.71 (m, 2H),3.63 (t, J = 5.4 Hz, 2H), 1.77-1.56 (m, 4H), 1.51 (d, J = 2.9 Hz, 4H). Mass spectrometry: m/z: calcd for [C24H28OP]+ ([M]+), 363.19; found, 363.16 (Supplementary Fig. 3a).
0.95 mmol	In acetonitrile for 48h; Inert atmosphere; Reflux;	(6-hydroxyhexyl)triphenylphosphonium bromide (TPP) synthesis To a stirred solution of 6-bromohexan-l-ol (5.0 g, 27.61 mmol) in 70 mL of acetonitrile at room temperature was added triphenylphosphine (7.967 g, 30.37 mmol) and the reaction mixture was refluxed for 48 h under a nitrogen atmosphere. Completion of the reaction was confirmed by thin layer chromatography (TLC). Then, the solvent was evaporated under reduced pressure, the crude product was washed with ethanol (2 x 30 mL), and the solid was dried under high vacuum without further purification to afford the title compound (0.95 mmol) as a white solid. The product was confirmed by NMR and LC MS. 1H MR (400 MHz, CDCb) d 7.92 - 7.75 (m, 9H), 7.71 (td, J = 7.5, 3.4 Hz, 6H), 3.87 - 3.71 (m, 2H), 3.63 (t, J = 5.4 Hz, 2H), 1.77 - 1.56 (m, 4H), 1.51 (d, J = 2.9 Hz, 4H). Mass m/z: calcd for [C24H2sOP]+ [M]+, 363.19; found, 363.16.

Yield	Reaction Conditions	Operation in experiment
95%	With 1H-imidazole In dichloromethane at 20℃;
85%	With 1H-imidazole In tetrahydrofuran at 0℃; for 1.5h; Inert atmosphere;
82%	With dmap; triethylamine In dichloromethane at 25℃; for 12h;

35%	With triethylamine In dichloromethane at 20℃;
	With 1H-imidazole In dichloromethane

Yield	Reaction Conditions	Operation in experiment
100%	With aluminum oxide for 0.05h; microwave irradiation;
100%	In N,N-dimethyl-formamide for 0.00833333h; microwave irradiation;
98.8%	In N,N-dimethyl-formamide at 20℃;	4 4. Preparation of small molecule S-1 6-Bromo-1-hexanol (26.0 g, 0.14 mol) was dissolved in 500 mL DMF. Then potassium thioacetate (32.8g, 0.29mol) was added and stirred at room temperature overnight. The reaction mixture was diluted with 500 mL EA and washed with 3×500 mL saturated aqueous NH4Cl to remove DMF. The upper phase was collected and dried with anhydrous Na2SO4. The solvent was evaporated to obtain S-1 as a colorless oily liquid (25.0 g, yield 98.8%).

93%	In N,N-dimethyl-formamide at 20℃; for 20h;
93%	With 18-crown-6 ether In toluene for 2h; Reflux;	3.1 2.3.1. 6-Acetylthiohexanol Potassium thioacetate (9.42 g, 82.5 mmol), 6-bromohexanol (10.00 g, 55.2 mmol) and 18-crown-6 (2.18 g, 8.2 mmol) were dissolved in toluene (500 mL) and stirred under reflux for 2 h. The reaction mixture was allowed to cool down to room temperature and the yellow precipitate was removed by filtration. The resulting red filtrate was washed with saturated aqueous solution of NaHCO3 (2 x 50 mL), saturated aqueous solution of NaCl (1 x 50 mL) and water (1 x 50 mL). The organic phase was dried over MgSO4 and the solvent was removed under reduced pressure. (9.05 g, 93 %). 1H NMR (CDCl3):δ = 3.55 (tr, 2H, -CH2-OH), 2.80 (tr, 2H, -CH2-S-), 2.25 (s, 3H, -CO-CH3), 1.49 (m, 4H, -CH2-), 1.31 (m, 4H, -CH2-) ppm. 13C NMR (CDCl3): δ = 196.3 (-CO-S-), 62.6 (-CH2-OH), 32.5-25.2 (-CH2-), 30.6 (CH3-CO-) ppm.
91%	In N,N-dimethyl-formamide at 20℃; for 20h;
90%	In N,N-dimethyl-formamide at 20℃; for 16h; Molecular sieve;
86%	In N,N-dimethyl-formamide at 20℃; for 12h;	1-1 Synthesis of S-6-hydroxyhexyl ethanethioate (2) At room temperature, potassium ethanethioate (6.31 g, 55.2 mmol) was added slowly dropwise to a solution of 1-bromohexanol (1) (5.00 g, 27.6 mmol) in DMF (50 mL) while the solution was stirred. The reaction mixture as stirred for 12 hours, and then diluted with distilled water (30 mL). The mixture was extracted with Et2O (3*30 mL), and the organic layers were combined, dried with anhydrous MgSO4, filtered, and then concentrated. The concentrate was separated by column chromatography (hexane:EtOAc=2:1-1:1) to obtain compound 2 (4.20 g, 86%) as a light yellow liquid.
63%	In acetone at 40℃; for 18h;

Yield	Reaction Conditions	Operation in experiment
100%	With dmap; sodium carbonate In toluene for 1h; Cooling with ice;	120.1 (1) Production of 6-bromohexyl To a reaction flask, 93.3 g (515 mmol) of 6-bromo-1-hexanol, 65.5 g (618 mmol) of anhydrous sodium carbonate, 6.3 g (52 mmol) of N,N-dimethyl-4-aminopyridine and 515 mL of toluene were added. While the mixture was stirred under ice cooling, 59.6 g (584 mmol) of acetic anhydride was added dropwise thereto. After the completion of the dropwise addition, the mixture was stirred for 1 hour under ice cooling. The resultant reaction mixture was washed successively with water twice, with dilute hydrochloric acid and then with water. The toluene was distilled off under reduced pressure to obtain 114.9 g of 6-bromohexyl acetate. Yield: quantitative.
98%	With pyridine at 20℃; for 12h;
96%	In tetrahydrofuran at 30℃; for 0.5h;

[ CAS No. 4286-55-9 ] {[proInfo.proName]}

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94%	With melamine-N₂,N₄,N₆-trisulfonic acid In dichloromethane at 20℃; Inert atmosphere;	Acetylation of the ω-bromoalkanols with MTSA (melamine trisulfonic acid) [25] - General procedure General procedure: 6-Bromo-1-hexanol (1a) (29.3 g, 162 mmol) and MTSA (17.9 g, 49 mmol) were dissolved together in 400 mL of CH2Cl2. Acetic anhydride (17 mL, 181 mmol) was added and the mixture was stirred at rt. After completion of the reaction, as monitored by thin-layer chromatography, the mixture was filtered. The organic layer was washed with a 5% NaHCO3 solution and water, and dried over MgSO4. Concentration of the organic layer under reduced pressure gave the crude acetylated product with minor impurities. Purification was performed either by Kugelrohr distillation or by column chromatography (silica, eluent hexanes-ethyl acetate, 80-20). Kugelrohr distillation (110 °C, 0.079 mbar) afforded a pure colorless liquid of 6-bromohexyl acetate (2a) (33.9 g, 94%).6-Bromohexyl acetate (2a). 1H NMR (CDCl3, 300 MHz): δ = 1.34-1.44 (m, 4H), 1.61 (q, JH-H = 7.3 Hz, 2H), 1.83 (q, JH-H = 6.7 Hz, 2H), 2.01 (s, 3H), 3.37 (t, JH-H = 6.9 Hz, 2H), 4.02 (t, JH-H = 6.7 Hz, 2H); 13C NMR (CDCl3, 75 MHz): δ = 171.9, 65.0, 34.4, 33.3, 29.1, 28.4, 25.8, 21.7; FT-IR (NaCl, cm-1): υmax = 2938, 2860, 1740 (CO), 1462, 1438, 1388, 1366, 1244, 1046, 970, 889, 761, 729, 642.
89%	In acetonitrile at 20℃; for 2h;

Yield	Reaction Conditions	Operation in experiment
43%	With boron trifluoride diethyl etherate In dichloromethane at 20℃; for 1h; Molecular sieve; Inert atmosphere; Cooling with ice;	1,2,3,4,6-penta-acetyl-β--glucopyranose 1 (2g) and an appropriate amount of 4A molecular sieves were obtained in a round-Under the protection of nitrogen, dichloromethane was added,After stirring, add 1-bromo-6-hexanol 0.74 mL in an ice bath,Under the protection of nitrogen, 2.5 mL of boron trifluoride diethyl ether was added dropwise,lh after the withdrawal of ice bath to room temperature reaction, to be TLC monitoring raw materials after the reaction is complete,Add water to stop antiShould be diluted with the appropriate amount of methylene chloride,With a saturated NaHC03 solution to adjust the pH of about 7, dichloromethane extraction, saturated brine washing anhydrous Na2S04 drying, filtration, concentration, column chromatography can be white solid compounds 2,3,4,6-tetra-acetyl (6-bromohexyl) -β--glucopyranoside 2 (990.3 mg, 43%)
36%	With boron trifluoride diethyl etherate In dichloromethane for 1h;
36%	With boron trifluoride diethyl etherate In dichloromethane at 0 - 20℃; for 4h;

Yield	Reaction Conditions	Operation in experiment
99%	With potassium carbonate In N,N-dimethyl-formamide for 18h; Reflux;
73%	Stage #1: p-Iodophenol With potassium hydroxide In dimethyl sulfoxide for 0.166667h; Inert atmosphere; Stage #2: 1-bromo-6-hexanol In dimethyl sulfoxide for 8h; Inert atmosphere;	4.1.9. 6-(4-Iodophenoxy)hexan-1-ol 18 4-Iodophenol (3.0 g, 13.64 mmol) and potassium hydroxide (1.68 g, 30.0 mmol) were dissolved in 15 mL of DMSO. After stirring for 10 min 6-bromo-1-hexanol (1.96 ml, 15.0 mmol) was added dropwise. After 8 h, the reaction was quenched by adding an aqueous solution of 5% HCl. The product was extracted with dichloromethane (3×50 mL). The organic phases were washed thrice with a saturated solution of NaCl and after dried over anhydrous Na2SO4. The solvent was evaporated at reduced pressure. The crude product was purified by silica gel column chromatography (dichloromethane/ethyl acetate 7:3 as eluent) obtaining 6-(4-iodo-phenoxy)-hexan-1-ol 18 (3.202 g, 73%) as a colourless oil.24 (Found: C, 45.04, H, 5.33. C12H17IO2 requires C, 45.02, H, 5.35); Rf (dichloromethane/ethyl acetate 7:3) 0.55; δH (CDCl3, 400 MHz): 1.26 (1H, t, J 7.1 Hz, OH), 1.33-1.54 (4H, m, CH2), 1.60 (2H, quintet, J 7.1 Hz, CH2), 1.78(2H, quintet, J 6.5 Hz, CH2), 3.65 (2H, t, J 6.6 Hz, CH2), 3.91 (2H, t, J 6.5 Hz, CH2), 6.61-6.71 (2H, app d, J 9 Hz, Ph), 7.50-7.58 (2H, app d, J 9 Hz, Ph) ppm.4.1.10.
69%	Stage #1: p-Iodophenol With sodium hydroxide In tetrahydrofuran; N,N-dimethyl-formamide at 20℃; for 0.25h; Stage #2: 1-bromo-6-hexanol In tetrahydrofuran; N,N-dimethyl-formamide at 20 - 60℃;	5.1 Example 5.1; Synthesis dof 6-(4-iodophenoxy)hexan-l-ol; DMF, THFA solution of NaOH (0.327 g, 8.18 mmol) and 4-iodophenol (1.5 g, 6.82 mmol) in 7.5 ml of DMF and 3.5 ml of THF was stirred at room temperature for 15 minuts. Then bromohexanol (1.482 g, 8.18 mmol) was added and the reaction misture was warmed at 600C. When the reaction is over, water was added (15 ml) and the mixture was extracted with ethyl acetate. The organic phase was dried over anhydrous sodium sulphate and after filtration the solvent was removed at reduced pressure. The product was isolated by silica gel column chromatography using a mixture of ethyl acetate:dichloromethane 3:7 as eluant. A white solid was obtained (1.509 g, yield 69%).

Yield	Reaction Conditions	Operation in experiment
81%	With potassium carbonate In N,N-dimethyl-formamide at 90℃; for 10h;
67%	With potassium carbonate In acetone at 64℃; for 24h;	2.1 [Example 2]; Synthesis of compound (Z2); (1) Synthesis of compound (P2); [Show Image] In a 100-mL pear-shaped flask fitted with a condenser, 4-hydroxybenzaldehyde (6.1 g, 50 mmol), 6-bromo-1-hexanol (9.1 g, 50 mmol), potassium carbonate (13.8 g, 100 mmol) and acetone (100 mL) were placed and combined into a mixture. The mixture was subjected to a reaction at 64°C for 24 hours under stirring. After completion of the reaction, the solvent was distilled off under reduced pressure to obtain yellow wet solid. Subsequently, the solid and water (70 mL) were mixed. Diethyl ether (50 mL) was added, followed by extraction. The extraction was conducted three times. An organic layer was separated, to which anhydrous magnesium sulfate was added to dry the same. Subsequent to filtration, the solvent was distilled off under reduced pressure to obtain yellow solid. The solid was dissolved in ethyl acetate (5 mL), followed by purification by silica gel column chromatography (column: "Silica Gel 60", 0.063-0.200 mm, product of Merck & Co., Inc., eluent: hexane/ethyl acetate = 2/1). From the thus-obtained solution, the solvent was distilled off to obtain white solid (7.4 g). The results of a measurement of the solid by NMR are shown below. From the results, the white solid was confirmed to be the intermediate compound (P2) shown in the above-described synthesis scheme (yield: 67%). 1H-NMR(DMSO-d6) δ: 1.55(m,4H), 1.62(m,2H), 1.84(m,2H), 3.67(t,2H), 4.05(t,2H), 7.00(d,2H), 7.84(d,2H), 9.88(s,1H).
67%	With potassium carbonate In acetone at 64℃; for 24h;	(Polymerizable compound (RM8) synthesize) Was added 4-hydroxybenzaldehyde with a cooling tube in the lml eggplant type flask 6.1 g (5 Ommol), 6- 1-hexanol desert .1g (50mmol), potassium carbonate 13.8g (lOOmmol), and 100ml as a mixture of acetone at 64 ° C - side stirring for 24 hours to react. After completion of the reaction, the solvent was distilled off under reduced pressure to give a yellow the wet solid '. Thereafter the solid was mixed with water 7 0ml, 50ml of diethyl ether was added and extracted. It was extracted 3 times. The combined organic layer was separated, dried over anhydrous magnesium sulfate was added, filtered and the solvent was distilled off under reduced pressure to give a yellow solid. The solid was dissolved in ethyl acetate and 5ml, to column chromatography (column: silica gel 60 0.063 -0.200mmThe prepared solution φ Merck eluent: hexane / ethyl acetate = 2/1) for purification. Obtained from a solution of this solvent was evaporated to give a white solid 7.4g. The solid results were measured by NMR of as follows. The results of the white solid was confirmed by the following reaction formula as the compound (RM8-A) in Fig. The yield was 67%.

44%	With sodium hydroxide In ethanol for 48h; Heating;
	With potassium carbonate In N,N-dimethyl-formamide at 90℃;

Yield	Reaction Conditions	Operation in experiment
42%	With potassium iodide; potassium hydroxide In ethanol at 60 - 90℃; for 10h;	4 After dissolving 17 g (79.5 mmol) of 4-(4-hydroxyphenyl)benzoic acid and 16.4 g (91 mmol) of 6-bromohexanol in 200 ml of ethanol, one spatula of potassium iodide was added, and the mixture was heated at 60°C and stirred. Also, a solution of 8 g (140 mmol) of potassium hydroxide in 20 ml of ethanol was slowly added dropwise, and the mixture was heated and stirred at 90°C for 10 hours. Upon completion of the reaction, the solvent was distilled off under reduced pressure, and then 500 ml of water was added to the reaction mixture, the pH was adjusted, and the precipitate was filtered to obtain a white solid. This was dried under reduced pressure, and then the recovered white solid was washed with methanol to obtain 10.6 g (33.5 mmol) of 4-(6-hydroxyhexyloxy)biphenyl-4'-carboxylic acid as a white powder. (Yield: 42%) · Measured values: 1H-NMR (δ, DMSO-d6): 1.40-1.87 (8H, m), 4.10 (2H, t), 4.22 (2H, t), 7.12 (2H, d), 7.74 (2H, d), 7.81 (2H, d), 8.09 (2H, d), 10.7 (1H, s)· Calculated: C19H23O4 (315): C, 72.36%; H, 7.35%; O, 20.29%· Found: C, 72.70%; H, 6.90%; O, 20.40%
40%	With potassium hydroxide; potassium iodide In methanol; water for 24h;

Yield	Reaction Conditions	Operation in experiment
82%	With potassium carbonate In acetone at 80℃; for 30h;	7-(2-Hydroxyethoxy)4-methylcoumarin (2b) General procedure: A solution of 2-bromoethanol (1.36 mL, 19 mmol), 7-hydroxy-4-methylcoumarin (2a, 2.33 g,13 mmol), potassium carbonate (8.32 g, 60 mmol), and acetone (50 mL) was heated at 80 °C for 30 h. The cooled reaction solution was filtered and then evaporated under vacuum. The crude product was purified using column chromatography on silica gel with ethyl acetate as eluent; yield 91%.
80%	With potassium carbonate In N,N-dimethyl-formamide at 60℃;
71%	With potassium carbonate In N,N-dimethyl-formamide at 60℃; for 3h;

Yield	Reaction Conditions	Operation in experiment
90%	With potassium carbonate In acetone at 64℃; for 24h;	1.1 7.61 g (50.0 mmol) of methyl 4-hydroxybenzoate, 9.1 g (50.0 mmol) of 6-bromo-1-hexanol, 13.8 g (100 mmol) of potassium carbonate and 70 ml of acetone were added to a 200 ml round bottom flask equipped with a condenser to provide a mixture, followed by reaction under stirring at 64°C for 24 hours. After completion of the reaction, the reaction solution was filtered under reduced pressure and the solvent was distilled off under reduced pressure to obtain a yellow wet solid. This solid was purified by silica gel column chromatography (column: silica gel 60, 0.063-0.200 mm, made by Merck & Co., eluate: hexane/ethyl acetate = 1/1). The solvent was distilled off from the resulting solution to obtain 11.3 g of a white solid. This solid was subjected to measurement of NMR with the results shown below. From the results, it was confirmed that this white solid was made of the intermediate compound (P1) (yield: 90%). 1H-NMR(CDCl3) δ: 1.3-1.7(m, 8H), 3.67(m, 2H), 3.88(s, 3H), 4.03(t, 2H), 6.91(d, 2H), 7.99(d, 2H).
90%	With potassium carbonate In acetone at 64℃; for 24h;	3.A3 Synthetic Examples 3 Synthesis of polymerizable liquid crystal compound (E3) [Show Image] 7.61 g (50.0 mmol) of methyl 4-hydroxybenzoate, 9.1 g (50.0 mmol) of 6-bromo-1-hexanol, 13.8 g (100 mmol) of potassium carbonate and 70 ml of acetone were added to a 200-ml round-bottomed flask equipped with a condenser tube to provide a mixture, followed by reaction under agitation at 64°C for 24 hours. After completion of the reaction, the solution was filtered under reduced pressure and the solvent was distilled off under reduced pressure to obtain a yellow wet solid. Thereafter, this solid was purified by silica gel column chromatography (column: silica gel 60, 0.063 to 0.200 mm, made by Merck KGaA, eluate: hexane/ethyl acetate = 1/1). The solvent was distilled off from the resulting solution to obtain 11.3 g of a white solid. The results of NMR measurement of the solid are indicated below. From the results, it was confirmed that this white solid was an intermediate compound (A3) (yield: 90%). 1H-NMR (CDCl3) δ:1.3-1.7 (m, 8H), 3.67 (m, 2H), 3.88 (s, 3H), 4.03 (t, 2H), 6.91 (d, 2H), 7.99 (d, 2H).
90%	With potassium carbonate In acetone at 64℃; for 24h;	(Polymerizable compound (RM5) synthesize) 4-hydroxy-methyl-benzoic acid 7.61g (50.0mmol) attached to the cooling pipe 200ml eggplant-shaped flask, 6 - bromo-1-hexanol 9.1g (50.0mmol), potassium carbonate 13.8g (100mmol), and 70ml as a mixture of acetone at 64 ° C- side stirring for 24 hours to react. After completion of the reaction, the reaction solution was filtered under reduced pressure, the solvent was distilled off under reduced pressure to give a yellow wet solid. The solid by silica gel column chromatography (column: silica gel 60,0.063-.200mm, Merck system, eluent: hexyl hospital / ethyl acetate = 1/1 (ν / ν)) for purification. The solvent was evaporated from a solution of the resulting white solid 1 1.3g. The solid NMR measurement results are shown below. The knotIf confirmed by the following reaction of the white solid compound of formula RM5-A). The yield was 90%.

90%	With potassium carbonate In acetone at 64℃; for 24h;	1 Synthesis of Compound (P1) In a 200 ml Nasar flask equipped with a cooling tube,7.61 g (50.0 mmol) of methyl 4-hydroxybenzoate, 9.1 g (50.0 mmol) of 6-bromo-1-hexanol,13.8 g (100 mmol) of potassium carbonate,And acetone (70 ml) were added to the mixture,The reaction was carried out with stirring at 64 DEG C for 24 hours.After completion of the reaction,The reaction solution was filtered under reduced pressure, the solvent was distilled off under reduced pressure,A yellow, wet solid was obtained.The solid was purified by silica gel column chromatography(Column: silica gel 60, 0.063-0.200 mm, solvent: eluent: hexane / ethyl acetate = 1/1)& Lt; / RTI & gt; The solvent was distilled off from the obtained solution, 11.3 g of a white solid was obtained. The result of measurement of this solid by NMR is shown below.From this result, it was confirmed that the white solid was the intermediate compound (P1) (yield: 90%).
86%	With potassium carbonate; potassium iodide In N,N-dimethyl-formamide at 90℃; for 48h;
72%	With potassium carbonate; potassium iodide In acetone for 24h; Inert atmosphere; Reflux;
	With potassium carbonate In butanone
	With potassium carbonate; potassium iodide In N,N-dimethyl-formamide
	With potassium carbonate; potassium iodide In N,N-dimethyl-formamide at 90℃;
		9 1.9. 1.9. Synthesis of methyl 4-[(6-hydroxyhexyl)oxy]benzoate 14 40.0 g (263 mmol) methyl 4-hydroxybenzoate and 43.6 g (315 mmol) are dissolved in 150 mL methyl(ethyl)ketone and 49.9 g (276 mmol) 6-bromohexan-1-ol are added and the reaction mixture is heated up to reflux and stirred for 16 h. The reaction mixture is then cooled to room temperature (RT) and the precipitating residue is filtered off, is washed with acetone and dried under vacuum. The crude product is crystallized at 5° C. out of toluene and the product can be used in the next step without further purification.

Yield	Reaction Conditions	Operation in experiment
92%	With pyridine In dichloromethane at 20℃; for 5h;	1.1 6-Bromo-1-hexanol (L) (99.2 g, 548 mmol, produced by Aldrich Co.) and methylene chloride (250 mL) were stirred together, and thereto pyridine (48.7 mL, 603 mmol) was added. Further, pivaloyl chloride (70.9 mL, 575 mmol) was added dropwise thereto while ice cooling, and then the resulting mixture was stirred for 5 hours at room temperature. The reaction solution obtained was washed with diluted hydrochloric acid and saturated brine for once each. The washed solution was dried over anhydrous magnesium sulfate and then concentrated to yield a crude product. The crude product obtained was purified by silica gel column chromatography (eluate: 9:1 mixture of hexane with ethyl acetate) to give 134 g of Intermediate (B) as an oily matter (in a 92% yield). NMR Spectrum of Intermediate (B) 1H-NMR (CDCl3): δ 1.20 (s, 9H), 1.30-1.50 (m, 4H), 1.65 (m, 2H), 1.88 (m, 2H), 3.41 (t, 2H), 4.07 (t, 2H)
91%	With dmap; triethylamine In dichloromethane at 20℃;
72%	With triethylamine In dichloromethane at 0 - 20℃; for 12h; Inert atmosphere;