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Product Details of [ 4224-70-8 ]

CAS No. :4224-70-8 MDL No. :MFCD00004422
Formula : C6H11BrO2 Boiling Point : -
Linear Structure Formula :- InChI Key :NVRVNSHHLPQGCU-UHFFFAOYSA-N
M.W : 195.05 Pubchem ID :20210
Synonyms :

Calculated chemistry of [ 4224-70-8 ]

Physicochemical Properties

Num. heavy atoms : 9
Num. arom. heavy atoms : 0
Fraction Csp3 : 0.83
Num. rotatable bonds : 5
Num. H-bond acceptors : 2.0
Num. H-bond donors : 1.0
Molar Refractivity : 40.6
TPSA : 37.3 Ų

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) : -6.76 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.71
Log Po/w (XLOGP3) : 1.03
Log Po/w (WLOGP) : 2.03
Log Po/w (MLOGP) : 1.79
Log Po/w (SILICOS-IT) : 1.58
Consensus Log Po/w : 1.63

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 1.0
Bioavailability Score : 0.56

Water Solubility

Log S (ESOL) : -1.37
Solubility : 8.35 mg/ml ; 0.0428 mol/l
Class : Very soluble
Log S (Ali) : -1.4
Solubility : 7.71 mg/ml ; 0.0395 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -2.13
Solubility : 1.43 mg/ml ; 0.00735 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 1.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 2.19

Safety of [ 4224-70-8 ]

Signal Word:Danger Class:8
Precautionary Statements:P280-P305+P351+P338-P310 UN#:3261
Hazard Statements:H314 Packing Group:
GHS Pictogram:

Application In Synthesis of [ 4224-70-8 ]

* 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 [ 4224-70-8 ]
  • Downstream synthetic route of [ 4224-70-8 ]

[ 4224-70-8 ] Synthesis Path-Upstream   1~32

  • 1
  • [ 4224-70-8 ]
  • [ 4101-68-2 ]
Reference: [1] Naturwissenschaften, vol. 44>1957>89,
[2] Canadian Journal of Chemistry, 1962, vol. 40, p. 1846 - 1850
  • 2
  • [ 4224-70-8 ]
  • [ 818-88-2 ]
  • [ 26825-90-1 ]
  • [ 106-79-6 ]
  • [ 1472-93-1 ]
  • [ 4101-68-2 ]
Reference: [1] Canadian Journal of Chemistry, 1964, vol. 42, p. 1788 - 1791
  • 3
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  • [ 6621-59-6 ]
Reference: [1] Journal of the American Chemical Society, 1945, vol. 67, p. 687
[2] Helvetica Chimica Acta, 1983, vol. 66, # 7, p. 2294 - 2307
  • 4
  • [ 502-44-3 ]
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YieldReaction ConditionsOperation in experiment
92% With sulfuric acid; hydrogen bromide In water for 12 h; Inert atmosphere; Reflux General procedure: Typical procedure: Under a dry argon atmosphere, 48percent HBr aqueous solution (41.0mL, 360mmol) and conc. sulfuric acid (9.6mL) were added dropwise to γ-butyrolactone (3a) (6.10g, 70.9mmol), and the resulting mixture was left undisturbed at room temperature for 2h. Then, after refluxing for 12h, the reaction mixture was cooled to room temperature. To this reaction mixture, 192mL of water was added, and the crude product was extracted with diethyl ether. The combined organic layer was washed with brine, dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography eluted with a mixed solvent of ethyl acetate/hexane (1/2v/v). The fraction with an Rf value of 0.44 was collected and dried under reduced pressure to afford 4-bromobutanoic acid (4a) as yellow oil (7.638g, 65percent)
82% at 20℃; for 7 h; Reflux General procedure: 4-Butyrolactone (1) (48.2 g, 0.56 mol, 1 equiv) was dissolved in a mixture of 48percent HBr solution (317 mL, 2.8 mol, 5 equiv) and conc H2SO4 (76 mL, 1.4 mol, 2.5 equiv) and left at room temperature for 2 h. The mixture was refluxed for 5 h, cooled to room temperature and poured to 1.5 L distilled water. The mixture was extracted with diethyl ether, washed with brine, dried over Na2SO4 and concentrated. Distillation of the crude product under reduced pressure (7 mbar) gave 57.0 g (61percent) of colourless oil
Reference: [1] Reactive and Functional Polymers, 2016, vol. 99, p. 1 - 8
[2] Bioorganic and Medicinal Chemistry, 2011, vol. 19, # 1, p. 567 - 579
[3] Bioorganic and Medicinal Chemistry, 2006, vol. 14, # 9, p. 2896 - 2903
[4] Bioorganic and Medicinal Chemistry, 2006, vol. 14, # 23, p. 7681 - 7687
[5] Journal of the American Chemical Society, 1982, vol. 104, # 5, p. 1391 - 1403
[6] Journal of Organic Chemistry, 1975, vol. 40, # 23, p. 3456 - 3458
[7] Tetrahedron Letters, 1981, vol. 22, # 50, p. 5101 - 5104
[8] Journal of the American Chemical Society, 1981, vol. 103, # 17, p. 5183 - 5189
[9] Synthesis, 2008, # 20, p. 3229 - 3236
[10] Beilstein Journal of Organic Chemistry, 2011, vol. 7, p. 1342 - 1346
  • 5
  • [ 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
  • 6
  • [ 1191-25-9 ]
  • [ 4224-70-8 ]
YieldReaction ConditionsOperation in experiment
360 g at 70℃; The present embodiment provides a process for the preparation of 6-brominated triphenylphosphonium orthohexanoic acid, which comprises the steps of: Hydrolysis reaction: 500ml bottle into the 220g caprolactam, 140g sodium hydroxide, heated to reflux reaction for 5 hours, the reaction completed, add 230 water diluted to get the hydrolyzate To the 1000ml bottle, add 353g hydrolyzate, drop 230g 30percent industrial hydrochloric acid to adjust the pH to 4, pour out. Diazotization reaction: in 1000ml bottle by adding 150g water, 100g sodium nitrite, stirring dissolved, down to -5 ° C, at -5 ° C ~ 0 ° C dropping good pH hydrolyzate, 35min drop finished , Add drop at -5 ° C ~ 0 ° C for 5 hours, then add 42g 30percent of industrial hydrochloric acid, heated to reflux 13min to starch potassium iodide test paper unchanged blue, pH = 1, down to 25 ° C, transferred to Separate the funnel, divide the water layer below, and separate the upper reservoir. Bromination reaction: Add 200 g of the upper layer to the 1000 ml bottle, 500 g of 48percent hydrobromic acid, start stirring, add 94 g of concentrated sulfuric acid, raise the temperature to 70 ° C for 3.5 hours, drop to 45 °, transfer to the separatory funnel, Out of the upper oil about 360g (by 50percent content into the next step reaction). The lower layer of acid water was added to a 30percent solution with a pH of 7percent (96percent of caustic soda). 4, 6-brominated triphenylphosphonium n-hexanoic acid synthesis: 1000ml bottle by adding 180g of the previous bromine oil, 370g toluene, 136g triphenyl phosphorus, temperature reflux reaction 3 hours, cooling and crude crude. efined: by the crude: methanol (m: m) = 1: 0.6 all dissolved, then add 5 times the crude amount of ethyl acetate, stir, add 13percent times the crude activated carbon, filter, the filtrate plus 6 times In the crude amount of ethyl acetate will be finished all the finished product, filtered and dried finished product, the mother liquor washed away after the methanol off the water recovery of ethyl acetate.
Reference: [1] Tetrahedron Asymmetry, 1998, vol. 9, # 8, p. 1345 - 1350
[2] Journal of the Chemical Society, 1949, p. 1475
[3] Journal of the American Chemical Society, 1944, vol. 66, p. 839
[4] Beilstein Journal of Organic Chemistry, 2011, vol. 7, p. 1342 - 1346
[5] Patent: CN106632474, 2017, A, . Location in patent: Paragraph 0048-0055; 0056-0063; 0064-0071; 0072-0079
  • 7
  • [ 6066-82-6 ]
  • [ 4286-55-9 ]
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  • [ 42014-54-0 ]
Reference: [1] Angewandte Chemie - International Edition, 2002, vol. 41, # 21, p. 4059 - 4061
  • 8
  • [ 55975-26-3 ]
  • [ 700-58-3 ]
  • [ 21898-84-0 ]
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  • [ 56820-19-0 ]
Reference: [1] Journal of Organic Chemistry, 2005, vol. 70, # 13, p. 5103 - 5110
  • 9
  • [ 57978-00-4 ]
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  • [ 1233324-44-1 ]
Reference: [1] Journal of the American Chemical Society, 2010, vol. 132, # 27, p. 9236 - 9239
  • 10
  • [ 42014-54-0 ]
  • [ 4224-70-8 ]
Reference: [1] Angewandte Chemie - International Edition, 2002, vol. 41, # 21, p. 4059 - 4061
  • 11
  • [ 629-11-8 ]
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Reference: [1] Bulletin of the Chemical Society of Japan, 1986, vol. 59, # 11, p. 3535 - 3539
[2] Tetrahedron Asymmetry, 2003, vol. 14, # 13, p. 1799 - 1806
[3] Journal of the American Chemical Society, 1950, vol. 72, p. 5137
  • 12
  • [ 60-32-2 ]
  • [ 4224-70-8 ]
Reference: [1] Patent: WO2007/117404, 2007, A2, . Location in patent: Page/Page column 21; 27-28
[2] Patent: CN106632474, 2017, A,
  • 13
  • [ 6621-59-6 ]
  • [ 4224-70-8 ]
Reference: [1] Journal of the American Chemical Society, 1968, vol. 90, p. 3533 - 3537
[2] Journal of Organic Chemistry, 1964, vol. 29, p. 1001 - 1003
  • 14
  • [ 642470-70-0 ]
  • [ 4224-70-8 ]
Reference: [1] Journal of the American Chemical Society, 1924, vol. 46, p. 2841
  • 15
  • [ 82258-18-2 ]
  • [ 4224-70-8 ]
Reference: [1] Journal of the American Chemical Society, 1927, vol. 49, p. 1829
  • 16
  • [ 2408-01-7 ]
  • [ 4224-70-8 ]
Reference: [1] Bulletin of the Academy of Sciences of the USSR, Division of Chemical Science (English Translation), 1984, vol. 33, # 11, p. 2407 - 2409[2] Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, 1984, # 11, p. 2628 - 2630
  • 17
  • [ 111-24-0 ]
  • [ 143-33-9 ]
  • [ 4224-70-8 ]
Reference: [1] Journal of the American Chemical Society, 1924, vol. 46, p. 2841
  • 18
  • [ 105-60-2 ]
  • [ 4224-70-8 ]
Reference: [1] Tetrahedron, Supplement, 1966, vol. 8, p. 313 - 319
[2] Journal of Organic Chemistry USSR (English Translation), 1966, vol. 2, # 11, p. 1990 - 1992[3] Zhurnal Organicheskoi Khimii, 1966, vol. 2, # 11, p. 2028 - 2031
[4] Patent: CN106632474, 2017, A,
  • 19
  • [ 34957-71-6 ]
  • [ 4224-70-8 ]
Reference: [1] Annales de Chimie (Cachan, France), 1957, vol. <13>2, p. 682,700
  • 20
  • [ 14273-90-6 ]
  • [ 4224-70-8 ]
Reference: [1] Gazzetta Chimica Italiana, 1960, vol. 90, p. 1299 - 1306
  • 21
  • [ 108-94-1 ]
  • [ 4224-70-8 ]
Reference: [1] Journal fuer Praktische Chemie (Leipzig), 1970, vol. 312, p. 1058 - 1062
  • 22
  • [ 512-85-6 ]
  • [ 110-54-3 ]
  • [ 1577-22-6 ]
  • [ 10035-10-6 ]
  • [ 4224-70-8 ]
Reference: [1] Journal of the American Chemical Society, 1943, vol. 65, p. 684
[2] Journal of the American Chemical Society, 1945, vol. 67, p. 2279
  • 23
  • [ 1577-22-6 ]
  • [ 10035-10-6 ]
  • [ 4224-70-8 ]
Reference: [1] Journal of the Chemical Society, 1934, p. 1998
  • 24
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  • [ 14273-90-6 ]
YieldReaction ConditionsOperation in experiment
90% With hydrogen chloride (gas) In methanol 1.
Preparation of methyl 6-bromocaproate (methyl 6-bromohe:Kanoate).
Hydrogen chloride (gas) was added to a solution of 5.01 g (25.7 mmol) of 6-bromocaproic acid in 250 ml of methanol via vigorous bubbling for 2-3 minutes.
The mixture was stirred at 15-25° C. for 3 hours and then concentrated to afford 4.84 g of the product as a yellow oil (90percent):
H-NMR (DMSO) 3.58 (3H, s), 3.51 (2H, t), 2.29
(2H, t), 1.78 (2H, pentet), and 1.62-1.27 ppm (4H, m).
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[2] Patent: US4436746, 1984, A,
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[4] Patent: EP2425861, 2012, A1,
[5] Patent: US2012/65367, 2012, A1,
  • 25
  • [ 67-56-1 ]
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YieldReaction ConditionsOperation in experiment
100% Heating / reflux To a solution 6-bromohexanoic acid (10 g, 50 mmol) in MeOH was added few drops of concentrated H2SO4. The mixture was then refluxed overnight. Methanol was EPO <DP n="83"/>evaporated and the residue was taken in dichloromethane and washed with saturated solution of sodium bicarbonate and dried over MgSO4. The solvent was then evaporated to give the desired ester (10.7 g) as slightly yellow oil in quantitative yield. 1H NMR: (CDCI3) δ (ppm): 3.6 (s, 3H); 3.3 (m, 2H); 2.4 (m, 2H); 1.5-1.8 (m, 4H); 1.3 (m, 2H).
100% at 20℃; Cooling with ice Synthesis of Methyl 6-bromohexanoate [0064] Add 6-bromohexanoic acid (4.1 g, 21.1 mmol) into 100 mL absolute methanol solution and then slowly drop 30 mL thionyl chloride into the solution with an ice bath. Stir the solution at room temperature overnight, concentrate the solution and add chloroform to dissolve. After suction filtration, take and concentrate the filtrate to get the product methyl 6-bromohexanoate (4.4 g, 100percent). Compound Data of the Product: [0065] IR (neat) v 11739 (CO) cm−1. [0066] 1H NMR (CDCl3) δ 3.64 (s, 3H, OCH3), 3.38 (t, 2H, BrCH2), 2.30 (t, 2H, CH2COOCH3), 1.82 (m, 2H, CH2CH2CH2CH2CH2), 1.63 (m, 2H, CH2CH2CH2CH2CH2), 1.46 (m, 2H, CH2CH2CH2CH2CH2). [0067] 13C NMR (CDCl3) δ 173.77 (CO), 51.73 (COOCH3), 33.72 (BrCH2), 33.34 (CH2CH2CH2CH2CH2), 32.30 (CH2CH2 CH2CH2CH2), 27.56 (CH2CH2CH2CH2CH2), 23.98 (CH2CH2CH2CH2CH2).
96% at 0 - 20℃; for 24 h; Inert atmosphere To a stirred solution of 6-bromohexanoic acid 24 (5.00 g, 25.6 mmol) in methanol (75 mL) at 0 °C, thionyl chloride (1.86 mL, 25.6 mmol) was added dropwise. The mixture was warmed to room temperature and stirred for 24 h. The solvent wasremoved in vacuo and the residue was dissolved in ethyl acetate (20 mL), washedwith water (2 x 10 mL), sat. NaHCO3 (10 mL), brine (10 mL) and dried (MgSO4).The solvent was removed in vacuo to give the title product 23 (5.13 g, 96°h) as ayellow oil which was used without further purification. 1H NMR (300 MHz; CDCI3)1.42-1.52 (2H, m, CH2), 1.56-1.66 (2H, m, CH2), 1.85-1.90 (2H, m, CH2), 2.33(2H, t, J = 3.0 Hz, CH2), 3.41 (2H, t, J = 6.0 Hz, CH2), 3.67 (3H, s, CH3). The 1H values are in agreement with literature.5
96% for 2 h; Heating / reflux 6-Bromohexanoic acid methyl ester (27a). To a solution of acetyl chloride (1. 0 mL, 14 mmol) in methanol (150 mL) at 0°C was added a solution of 6-bromohexanoic acid (10.0 g, 51 mmol) in methanol (50 mL). The mixture was heated at reflux for 2 hours, then allowed to cool down to room temperature and concentrated under reduced pressure. The residue was dissolved in ethyl acetate (150 mL) and washed consecutively with saturated aqueous sodium hydrogen carbonate (2 x 50 mL), distilled water (50 mL), and brine (50 mL). The organic layer was dried over anhydrous MgS04, filtered and concentrated under reduced pressure to give the title compound (10.3 g, 96percent) as a colourless oil.
93% for 8 h; Reflux 6-bromohexanoic acid 18 (4.886 g, 25.100 mmol) was dissolvedin methanol (75 mL). To this solution, Conc. H2SO4 (0.3 mL) was added and reaction mixture refluxed for 8 h. Then solvent evaporatedand residue was dissolved in ethyl acetate (200 mL). Theorganic part was then washed with saturated solution of NaHCO3(50 mL 3), dried and evaporated to give pure ester compound(4.626 g, 22.200 mmol). For making Wittig salt, bromo-estercompound was dissolved in dry CH3CN (70 mL) followed by additiontriphenylphosphine (7.000 g, 26.600 mmol). The reactionmixturewas then refluxed for 36 h. After that solvent evaporated togive gummy residue which was washed with hexanes (20 mL 3)to give compound 19.
92% Heating / reflux Example 15a; General Procedure for the Esterification of Bromoalkanoic Acids (I); Appropriate bromo alkanoic acid (1 equiv) was dissolved in methanol and a catalytic amount of conc.H2SO4 (0.1 mL/g) was added and the reaction mixture was refluxed for overnight. Upon reaction completion, methanol was removed in rotary evaporation and the crude product was washed with aq. NaHCO3, brine solution and extracted with ethyl acetate. The product was used further without column purification.; Example 15d; Synthesis of Methyl 6-Bromohexanoate (11); As mentioned in the general procedure (I), 6-bromohexanoic acid (15 g, 76.9 mmol, 1 equiv) was dissolved in methanol (150 mL), and a catalytic amount of conc.H2SO4 (2 mL) was added and the reaction was carried out. The product was taken to next step without column purification. Yield 14.8 g (92percent). 1H NMR (400 MHz, CDCl3): δ 3.66 (s, 3H), 3.42-3.38 (m, 2H), 2.32 (t, J=7.2 Hz, 2H), 1.90-1.83 (m, 2H), 1.68-1.61 (m, 2H), 1.50-1.44 (m, 2H). 13C NMR (100 MHz, CDCl3); δ 173.9, 51.5, 33.8, 33.4, 32.3, 27.6, 24.0. EI/MS m/z (r.i.) 211 (M+2, 98), 210 (M+1, 8), 209 (M+, 100), 178 (16), 161 (33), 129 (51), 97 (28), 87 (9), 74 (23), 69 (23).
91% at 0 - 20℃; Step 1
Methyl 6-bromohexanoate:
At about 0° C., thionyl chloride (11.9 g; 100 mmol; 1.00 equiv) was added dropwise to a stirred solution of 6-bromohexanoic acid (19.5 g; 100 mmol; 1.00 equiv) in methanol (100 mL).
The resulting solution was stirred at ambient temperature for about 1 hour and then concentrated in vacuo, to give the title product as a colorless oil (19 g; 91percent yield).
1H NMR (300 MHz, CDCl3) δ 3.68 (s, 3H), 3.41 (t, J=6.6 Hz, 2H), 2.43 (t, J=6.6 Hz, 2H), 1.88 (m, 2H), 1.64 (m, 2H), 1.49 (m, 2H).
87% for 16 h; Reflux; Inert atmosphere General procedure: Typical procedure: After refluxing the mixture of 4a (7.64g, 45.7mmol), methanol (78.4mL), and conc. sulfuric acid (0.77mL) for 16h under a dry argon atmosphere, it was cooled to room temperature. Then, aqueous solution of sodium bicarbonate (78mL) was added to the reaction mixture and the crude product was extracted with ethyl acetate. After washing the combined organic layer with sodium bicarbonate aqueous solution, water, and brine, it was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography eluted with a mixed solvent of chloroform/methanol (10/1v/v). The fraction with an Rf value of 0.86 was collected and dried under reduced pressure to afford methyl 4-bromobutanoate (5a)

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YieldReaction ConditionsOperation in experiment
98% for 48 h; Heating / reflux A solution of6-bromohexanoic acid (10.00 g, 51.27 mmol) and triphenyl phosphine (14.12 g, 53.83 mmol) in freshly distilled acetonitrile (50 mL) was vigorously stirred and refluxed for 48 hours. The solution was allowed to come to ambient temperature and the Wittig salt was precipitated upon scratching the inside wall of the glass reaction vessel with a spatula. The white solid product was collected, washed with ether and filtered to provide the title compound in 98percent yield (22.87 g): 1H NMR (400 MHz1 CD3OD) δ 1.62-1.72 (m, 6H), 2.29 (t, 2H), 3.40-3.47 (m, 2H), 7.76-7.91 (m, 15H)
97.5% for 72 h; Reflux Triphenylphosphine (20 mg, 0.076 mmol) and 6-bromohexanoic acid (14.8 mg, 0.076 mmol) were dissolved in dry toluene (0.2 mL). The reaction mixture was refluxed over 72 hours. The solution was concentrated. The residue was washed consecutively with benzene (3 x 1 mL), hexane (1 mL), and Et20 (2 x 1 mL). The crystalline white solid was dried to give the pure product (28 mg, 97.5 percent). 1H NMR (300 MHz, CDC13) δ 7.80-7.68 (m, 15H), 3.58 (bs, 2H), 2.34-2.32 (m,2H), 1.63-1.57 (m, 6H). EI-MS (m z): Calcd for C24H2602P+ 377.16; found 377.1
95% for 20 h; Heating / reflux A solution of 6-bromohexanoic acid (3.9 g, 20.0 mmol, 1 equiv) in anhydrous acetonitrile (16 mL) was treated with triphenylphosphine (6.3 g, 24.0 mmol, 1.2 equiv) and warmed at reflux for 20 h. The reaction mixture was concentrated and the crude product was purified by column chromatography (SiO2, 5.5 x 8 cm, 50-100percent EtOAc-hexanes gradient and then 5percent MeOH-CH2Cl2) to afford Sl (8.7 g, 19.0 mmol, 95percent) as a white solid: 1H NMR (CDCl3, 400 MHz) δ 7.78-7.67 (m, 15H), 3.58 (m, 2H), 2.33 (m, 2H), 1.63 (m, 4H).
94% for 48 h; Inert atmosphere; Reflux General procedure: A mixture of ω-bromocarboxylic acid (1 equiv) and triphenylphosphine (1 equiv) in 300 mL of toluene was refluxed for 48 h under argon. The mixture was allowed to cool at room temperature and concentrated in vacuum. The residue was crystallized from various solvents to give the corresponding phosphonium salt.
91% for 24 h; Reflux Example 1
Synthesis of TPP-(CH2)5-COOH
A mixture of 6-bromohexanoic acid (2.0 g, 10.3 mmol) and TPP (2.8 g, 10.8 mmol) was heated to reflux for 24 h in acetonitrile.
The solvent was evaporated to dryness.
The resulting residue was washed with hexane-diethyl ether (3*30 mL) followed by vacuum drying to afford a white solid as a pure product. Yield: 91percent (4 g).
Melting point: 200-205° C.; 1H NMR (CDCl3): δ 9.3 (s, 1H), 7.6-7.8 (m, 15H), 3.5 (t, 2H), 2.3 (t, 2H), 1.6 (m, 6H).
13C NMR (CDCl3): δ 175, 135, 133.6, 130.6, 118.5, 34.2, 29.37, 23.9, 22.8, 22.29, 21.9. 31P NMR (CDCl3) 24.34. ppm. HRMS-ESI (m/z): [M-Br]+ calcd. for C24H26O2P+, 377.1665. found, 377.1629.
65% for 24 h; Inert atmosphere; Reflux Bromohexanoic acid (0.600 g, 3.076 mmol) and triphenylphosphine (0.968 g 3.691 mmol) were dissolved in 40 mL of acetonitrile.This reaction was refluxed for 24 h under a N2 environment. After 24 h, the solvent was evaporated to yield an oil, which was then precipitated with diethyl ether. The precipitate was filtered through a glass frit filter, and washed several times with diethyl ether to remove any impurities from the starting materials. The product was kept on vacuum for 1 h. Yield 0.760 g 65percent. 1H NMR (CDCl3, 400 MHz): δ 7.78 [m, 15H], 3.56 [m, 2H], 2.44 [m, 2H], 1.68 [m, 6H] ppm.
55% for 20 - 24 h; Heating / reflux A solution of 6-Bromohexanoic acid (3g, 0.0512 moles) and triphenylphosphine 4.8g, 0.018 moles) in dry acetonitrile (5OmL) was refluxed for 20-24 h and excess solvent was removed under reduced pressure to afford a color less oil which was triturated with dry benzene and wash in succession with dry benzene and ether (3 times each). During the washing procedure the material crystallized drying at reduced pressure afford Wittig salt as a white micro- crystalline powder (3.6g, 55percent yield).
55% Reflux A solution of 6-Bromohexanoic acid (3 g, 0.0512 moles) and triphenylphosphine 4.8 g, 0.018 moles) in dry acetonitrile (50 mL) was refluxed for 20-24 h and excess solvent was removed under reduced pressure to afford a color less oil which was triturated with dry benzene and wash in succession with dry benzene and ether (3 times each). During the washing procedure the material crystallized drying at reduced pressure afford Wittig salt as a white micro-crystalline powder (3.6 g, 55percent yield).

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