[ CAS No. 1707-77-3 ] {[proInfo.proName]}

Name: 1707-77-3|(1S,2S)-1,2-Bis((R)-2,2-dimethyl-1,3-dioxolan-4-yl)ethane-1,2-diol|95%
Brand: Ambeed
SKU: A158555
Price: 11.0 USD
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Rating: 97 (32 reviews)

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2D 3D

Structure of 1707-77-3 * Storage: {[proInfo.prStorage]}

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Quality Control of [ 1707-77-3 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 1707-77-3 ]

SDS Specification

Alternatived Products of [ 1707-77-3 ]

Product Details of [ 1707-77-3 ]

CAS No. :	1707-77-3	MDL No. :	MFCD00003211
Formula :	C₁₂H₂₂O₆	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	ODYBCPSCYHAGHA-ZYUZMQFOSA-N
M.W :	262.30	Pubchem ID :	96011
Synonyms :		Chemical Name :	(1S,2S)-1,2-Bis((R)-2,2-dimethyl-1,3-dioxolan-4-yl)ethane-1,2-diol

Calculated chemistry of [ 1707-77-3 ]

Physicochemical Properties

Num. heavy atoms :	18
Num. arom. heavy atoms :	0
Fraction Csp3 :	1.0
Num. rotatable bonds :	3
Num. H-bond acceptors :	6.0
Num. H-bond donors :	2.0
Molar Refractivity :	62.31
TPSA :	77.38 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	No
P-gp substrate :	Yes
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-8.25 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.63
Log Po/w (XLOGP3) :	-0.49
Log Po/w (WLOGP) :	0.01
Log Po/w (MLOGP) :	-0.47
Log Po/w (SILICOS-IT) :	0.99
Consensus Log Po/w :	0.53

Druglikeness

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

Water Solubility

Log S (ESOL) :	-0.96
Solubility :	28.8 mg/ml ; 0.11 mol/l
Class :	Very soluble
Log S (Ali) :	-0.67
Solubility :	56.4 mg/ml ; 0.215 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-0.52
Solubility :	79.8 mg/ml ; 0.304 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	0.0
Synthetic accessibility :	4.58

Safety of [ 1707-77-3 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P280-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H332-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 1707-77-3 ]

* 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 [ 1707-77-3 ]
Downstream synthetic route of [ 1707-77-3 ]

[ 1707-77-3 ] Synthesis Path-Upstream 1~8

1
[ 1707-77-3 ]
[ 23735-39-9 ]

Reference： [1] Bulletin of the Academy of Sciences of the USSR, Division of Chemical Science (English Translation), 1985, vol. 34, # 11, p. 2414 - 2415[2] Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, 1985, # 11, p. 2605 - 2606

2
[ 1707-77-3 ]
[ 641-74-7 ]

Reference： [1] Patent: WO2017/189477, 2017, A1, . Location in patent: Paragraph 0036; 0037

3
[ 1707-77-3 ]
[ 114746-70-2 ]

Reference： [1] Tetrahedron Letters, 1995, vol. 36, # 45, p. 8167 - 8170
[2] Organic Letters, 2011, vol. 13, # 21, p. 5788 - 5791

4
[ 1707-77-3 ]
[ 23788-74-1 ]

Reference： [1] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2002, vol. 41, # 3, p. 586 - 592
[2] Journal of Organometallic Chemistry, 1996, vol. 519, # 1-2, p. 93 - 101
[3] Helvetica Chimica Acta, 1989, vol. 72, # 6, p. 1301 - 1310
[4] Bulletin of the Academy of Sciences of the USSR, Division of Chemical Science (English Translation), 1985, vol. 34, # 11, p. 2414 - 2415[5] Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, 1985, # 11, p. 2605 - 2606
[6] Journal of Medicinal Chemistry, 1984, vol. 27, # 9, p. 1142 - 1149
[7] Chemical & Pharmaceutical Bulletin, 1981, vol. 29, # 12, p. 3593 - 3600
[8] Journal of Heterocyclic Chemistry, 1991, vol. 28, # 5, p. 1351 - 1355

5
[ 98-59-9 ]
[ 1707-77-3 ]
[ 23788-74-1 ]

Reference： [1] Angewandte Chemie, 1980, vol. 92, # 3, p. 201 - 202

6
[ 1707-77-3 ]
[ 83400-91-3 ]

Reference： [1] Journal of Organic Chemistry USSR (English Translation), 1990, vol. 26, # 11, p. 2070 - 2081[2] Zhurnal Organicheskoi Khimii, 1990, vol. 26, # 11, p. 2398 - 2411

7
[ 1707-77-3 ]
[ 52373-72-5 ]

Reference： [1] Journal of Organic Chemistry USSR (English Translation), 1990, vol. 26, # 11, p. 2070 - 2081[2] Zhurnal Organicheskoi Khimii, 1990, vol. 26, # 11, p. 2398 - 2411
[3] Bioorganic and Medicinal Chemistry, 2001, vol. 9, # 3, p. 773 - 783
[4] Synthesis, 1988, # 1, p. 54 - 56
[5] Angewandte Chemie - International Edition, 2015, vol. 54, # 34, p. 9898 - 9902[6] Angew. Chem., 2015, vol. 127, # 34, p. 10036 - 10040,5

8
[ 67-56-1 ]
[ 1707-77-3 ]
[ 52373-72-5 ]

Reference： [1] Synthesis, 1988, # 10, p. 790 - 792

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Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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Yield	Reaction Conditions	Operation in experiment
53%	With zinc(II) chloride In acetone at 20℃; for 22h;
	With hydrogenchloride; acetone
	With acetone; zinc(II) chloride

Yield	Reaction Conditions	Operation in experiment
85%	With triethylamine In dichloromethane at 0 - 20℃;
85%	With pyridine at 0℃; for 1.75h; Inert atmosphere;
70%	With triethylamine In dichloromethane for 2h; Ambient temperature;

Yield	Reaction Conditions	Operation in experiment
100%	With sodium (meta)periodate; Sodium hydrogenocarbonate In dichloromethane at 0 - 20℃; for 2h;
99%	With lead tetraacetate In ethyl acetate for 3h;
99%	With sodium (meta)periodate; Sodium hydrogenocarbonate In dichloromethane at 20℃; for 2h;

99%	With sodium (meta)periodate; Sodium hydrogenocarbonate In dichloromethane; water monomer at 20℃; for 1h;
99%	Stage #1: (1S,2S)-1,2-bis((R)-2,2-dimethyl-1,3-dioxolan-4-yl)ethane-1,2-diol With Sodium hydrogenocarbonate In dichloromethane at 23℃; for 0.166667h; Stage #2: With sodium (meta)periodate In dichloromethane for 3h;
98%	With sodium (meta)periodate; Sodium hydrogenocarbonate In dichloromethane at 20℃; for 1.5h;
98.4%	With tetrabutylammonium bromide; pyridinium chlorochromate at 20 - 25℃; for 3h;	1-8 Example 1 Add 200 g of dioxymethane to the clean reactor, put in 20 g of diacetone-D-mannitol under stirring, and control the temperature at 20 °C to 25 °C.Then, 0.2 g of tetrabutylammonium bromide and 17.9 g of oxidant PCC were added, and the temperature was controlled to keep the reaction at 20°C to 25°C for 3 hours. After the reaction was completed, suction filtration was performed to recover the solids in the reaction solution. , the collected filter was subjected to vacuum distillation to recover the solvent to obtain an oily product R-(+)-2,2-dimethyl-1,3-dioxolane-4-carbaldehyde 19.5g,The product yield was 98.4%, and the purity content was 99.7%
97.9%	With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; 18-crown-6 ether; Calcium Chloride-Oxygen In water monomer; ethyl acetate at 5 - 10℃; for 1.5h;	3 Example 3 200 g of ethyl acetate, 23 g of diacetone-D-mannitol, 0.6 g of 15-crown-5-ether, and TEMPO 0.5 g were sequentially added to a clean reactor.After stirring and mixing uniformly, the temperature was slowly lowered to 5 ° C, and 140 g of a calcium hypochlorite aqueous solution having a mass percentage of 10 wt% was added dropwise, and the temperature of the reaction system was controlled to be below 5 ° C during the dropwise addition. After the completion of the dropwise addition, the reaction was continued to make the temperature The oxidation reaction was carried out for 1.5 h at 5 ° C to 10 ° C. After the reaction was completed, it was allowed to stand and layer.The aqueous layer was removed, and the collected organic layer was washed once with 50 g of water, and the aqueous layer was separated by layering.The collected organic layer was added to 20 g of anhydrous sodium sulfate and stirred for 30 min.After suction filtration, the filtrate was collected, and the filtrate was concentrated under reduced pressure to remove solvent.After the obtained wet product is baked,Obtained 22.3 g of dry R-glyceraldehyde acetal,Yield 97.9%,The gas phase content was 99.5%.
96%	With sodium (meta)periodate; Sodium hydrogenocarbonate In dichloromethane at 20℃; for 1.5h;
95%	With sodium (meta)periodate; mesoporous silica In dichloromethane at 0℃; for 0.5h;
95%	With sodium (meta)periodate In dichloromethane; water monomer at 20℃; for 3h;
95%	With sodium (meta)periodate; Sodium hydrogenocarbonate In dichloromethane; water monomer for 2h;
94%	With sodium (meta)periodate; water monomer In dichloromethane at 20℃; for 2h;
94%	With sodium (meta)periodate; Sodium hydrogenocarbonate In dichloromethane at 5 - 20℃; for 2h;	1.1 Step 1. Synthesis of (4R)-2,2-dimethyl-1,3-dioxolane-4-carbaldehyde (C15) To a solution of (lS,2S)-l,2-bis[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]ethane-l,2-diol C14 (30 g, 114.4 mmol) in DCM (300 mL) was added NaHCCb (12 mL) and the mixture was cooled to 10 °C before NaI04 (49 g, 229.1 mmol) was added portion wise at such a rate that internal temperature stayed below 5 °C. The reaction was stirred at room temperature for 2 hours, then was filtered on Celite. The cake was washed with DCM and the filtrate was concentrated in vacuo , yielding (4R)-2,2-dimethyl-l,3-dioxolane-4-carbaldehyde (28.0 g, 94%) 1H NMR (400 MHz, DMSO-d6) δ 9.60 (s, 1H), 4.52 (ddd, J = 7.3, 4.6, 1.6 Hz, 1H), 4.13 - 4.05 (m, 2H), 1.38 (s, 3H), 1.33 (s, 3H).
94%	With sodium (meta)periodate; Sodium hydrogenocarbonate In dichloromethane at 5 - 20℃; for 2h;	1.1 Step 1. Synthesis of (4R)-2,2-dimethyl-1,3-dioxolane-4-carbaldehyde (C15) To a solution of (lS,2S)-l,2-bis[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]ethane-l,2-diol C14 (30 g, 114.4 mmol) in DCM (300 mL) was added NaHCCb (12 mL) and the mixture was cooled to 10 °C before NaI04 (49 g, 229.1 mmol) was added portion wise at such a rate that internal temperature stayed below 5 °C. The reaction was stirred at room temperature for 2 hours, then was filtered on Celite. The cake was washed with DCM and the filtrate was concentrated in vacuo , yielding (4R)-2,2-dimethyl-l,3-dioxolane-4-carbaldehyde (28.0 g, 94%) 1H NMR (400 MHz, DMSO-d6) δ 9.60 (s, 1H), 4.52 (ddd, J = 7.3, 4.6, 1.6 Hz, 1H), 4.13 - 4.05 (m, 2H), 1.38 (s, 3H), 1.33 (s, 3H).
93%	With sodium (meta)periodate In tetrahydrofuran; water monomer
92%	With sodium hydroxide; sodium (meta)periodate; potassium dihydrogen orthophosphate In dichloromethane; water monomer for 0.333333h; pH 7;
92%	With sodium (meta)periodate In dichloromethane for 0.333333h; Ambient temperature; pH 7;
91%	With sodium (meta)periodate; water monomer In dichloromethane at 32℃; for 1h;
90%	With sodium (meta)periodate In dichloromethane; water monomer
87%	With sodium (meta)periodate; mesoporous silica In dichloromethane at 0℃;
86%	With sodium (meta)periodate; Sodium hydrogenocarbonate In methylene chloride; water monomer at 20 - 25℃; for 2.33333h;	1.2 Step 2: Preparation of 2,2-dimethyl-[l,3]-dioxorane-4-carboaldehyde; 72.4 g of the compound obtained in Step 1 was dissolved in 724 ml of methylchloride, and 30 ml of saturated sodium bicarbonate was added thereto. The mixture was cooled in a water bath, and 118 g of sodium methaperiodate was added in small portion thereto over a period of 20 min while keeping the temperature at under 25°C. The reaction mixture was stirred at room temperature for 2 hours. After confirmng the completion of the reaction by thin layer chromatography (TLC), 36 g of anhydrous magnesiumsulfate was added to the reaction mixture, and stirred for 20 min. The resulting mixture was filtered and distilled under a reduced pressure at 30°C to remove the solvent, and the residue was further subjected in distillation under an atmospheric pressure at 55°C to completely remove the solvent. The reacting residue was distilled at 10 torr, about 40°C to obtain 61.6 g (yield 86%) of the title compound as a colorless liquid.NMR (300 MHz, CDC13): 1.41(s, 3H), 1.47(s, 3H), 4.07-4.19(m, 2H), 4.35~4.40(m, 1H), 9.71(s, 1H)
86%	With lead (IV) acetate In ethyl acetate at 20℃;
85%	With sodium (meta)periodate In tetrahydrofuran; water monomer for 4h;	2; 1.1 NaIO4 (16 g, 74.8 mmol) was added to a stirred solution of (1) (D-mannitol bisacetonide) (20 g, 76.2 mmol) in 9:1 THF- H2O (280 mL), and the resultant mixture was stirred for 4 h. The produced precipitate was filtered off, and most of THF was evaporated under reduced pressure. Then water (20 mL) was added and the aqueous solution was extracted with dichloromethane (6 X 50 mL). The combined organic extracts were dried over MgSO4 and solvent was removed to afford (2) ((R)-2,2-Dimethyl-1,3-dioxolane-4-carbaldehyde)(16.8 g, 85% yield), which was used in the next step without further purification. Characterization of (2): 1H-NMR (250 MHz, CDCl3) 1.4 (s, 3H), 1.5 (s, 3H), 4.1 (m, 2H), 4.4 (m, 1H), 9.7 (d, 3JH-H = 2 Hz, 1H).IR (film): 3417, 2985, 1735, 1372, 1064 cm-1.appearence: colourless oil.
84%	With sodium (meta)periodate; Sodium hydrogenocarbonate In water monomer at 35℃; for 2h;
83%	With sodium (meta)periodate; Sodium hydrogenocarbonate In dichloromethane; water monomer
82%	With lead tetraacetate
82%	With sodium (meta)periodate In dichloromethane; water monomer Ambient temperature;
82%	With NaIO₄*SiO₂ In dichloromethane at 20℃; for 1h; Inert atmosphere;
81%	With sodium (meta)periodate; Sodium hydrogenocarbonate In dichloromethane; water monomer for 3h;
80%	With sodium (meta)periodate; Sodium hydrogenocarbonate; magnesium(II) sulfate In dichloromethane for 0.166667h;
78%	With sodium (meta)periodate; Sodium hydrogenocarbonate In water monomer 1.) 10 deg C, 30 min; 2.) 3 h, room temp.;
77%	With sodium (meta)periodate; Sodium hydrogenocarbonate In dichloromethane
77%	With sodium (meta)periodate; mesoporous silica In dichloromethane at 0℃; for 0.5h;
77%	With sodium (meta)periodate; Sodium hydrogenocarbonate In dichloromethane at 25℃; for 2h;
76%	With lead tetraacetate; potassium carbonate
76%	With lead tetraacetate; potassium carbonate In chloroform at 0 - 20℃;
75%	With sodium (meta)periodate; mesoporous silica In dichloromethane; water monomer at 20℃; for 0.5h;
75%	With sodium (meta)periodate In dichloromethane	II Synthesis OF DIFLUORO ANALOGS OF LPA Another approach to the synthesis of difluoromethylene analogs of LPA is depicted in Figure 5. Synthesis of the target LPA analogues 10a and lOb (Figure 5) involved non-reductive deprotection of the penultimate dimethyl phosphates 9 with trimethylsilane bromide to permit incorporation of unsaturated acyl chains. The key step for the synthesis was the introduction of the difluoromethyl group by the 1,1- DIFLUORINATION OF A C-1 aldehyde. Thus, commercially-available D-mannitol 1,2 : 5,6- bis-acetonide was OXIDATIVELY cleaved with NAI04 to afford the acetonide-protected D-glyceraldehyde 2. 10 Addition of (diethylamino) sulfur trifluoride (DAST) to a solution of the aldehyde 2 in CH2C12 afforded the difluorinated compounds in high yield after purification by distillation under reduced pressure. Next, acidic cleavage of the acetonide-protecting group provided the diol intermediate 4. The crude diol obtained after removal of the acetonide was immediately converted to the bis-silyl ether 5, and the more labile TBDMS ether of the primary alcohol was cleaved selectively by treatment with a solution of pyridinium hydrofluoride in a mixture of pyridine and THF at rt. Initial attempts to obtain the primary alcohol 6 from bis-TBDMS ether 5, utilizing 4.0 eq. of pyridinium hydrofluoride resulted in disappointing yields (17%) after 48 h at rt. However, increasing to 6.0 equiv. gave the primary alcohol in good yield (73%) after 20 h at rt. The primary alcohol 6 was then phosphorylated with dimethylphosphoryl chloride in the presence of t-BuOK to give good yield of phosphate 7. The 2-TBDMS ether was further deprotected with tetra (N-BUTYL) ammonium fluoride (TBAF) in THF to give alcohol 8 in 72% yield; neutralization of TBAF with acetic acid permitted desilyation of the secondary alcohol without the migration of phosphate. DCC-promoted ESTERIFICATION of alcohol S with oleic acid or palmitic acid provided good yield of esters 9a and 9b, respectively. Importantly, the introduction of the acyl groups at this stage circumvents problems with acyl group migration during other synthetic operations. Finally, treatment of protected phosphates 9 with bromotrimethylsilane and subsequent addition of 5% aq. methanol provided the desired DIFLUORINATED LPA analogues 10 in essentially quantitative yield.(R)-Glyceraldehyde acetonide (2) was prepared from D-MANNITOL-L, 2: 5,6-bis- acetonide as DESCRIBEDLO to give aldehyde 2 as a clear liquid: [A] 20D : + 64.4 (lit. 19 [AD + 64. 9).
75%	With sodium (meta)periodate; Sodium hydrogenocarbonate In dichloromethane; water monomer for 3h;
75%	With sodium (meta)periodate; Sodium hydrogenocarbonate In dichloromethane; water monomer at 20℃; for 2h;
75%	With sodium (meta)periodate; mesoporous silica In dichloromethane; water monomer at 20℃; for 1h;	101.6 Step 6: (R)-2,2-Dimethyl-[l,3]dioxolane-4-carbaldehyde Sodium periodate (57.0 g, 270 mmol) was dissolved in hot water (115 mL) and silica (200 g, 60 A 220-440 mesh, particle size 35-75 μιη) was added. The mixture was stirred vigorously until a free flowing powder was obtained. This was added to a solution of 1,2:5,6-bis-O-(1-methylethylidene)-D-mannitol (50 g, 190 mmol) in dichloromethane (1.0 L) and the reaction was stirred at room temperature for 1 hour. The resultant mixture was filtered through a pad of Na2SO4 and the solids washed thoroughly with dichloromethane. The combined organic extracts were evaporated in vacuo to yield 37.2 g (75%) of the title compound as a colorless oil. 1H NMR (400 MHz, CDC13) δ 9.73 (d, J = 1.9 Hz, 1H), 4.38 (ddd, 7 = 7.4, 4.7, 1.9 Hz, 1H), 4.18 (dd, J = 8.8, 7.4 Hz, 1H), 4.10 (dd, J = 8.8, 4.7 Hz, 1H), 1.49 (s, 3H), 1.43 (s, 3H).
75%	With sodium (meta)periodate In dichloromethane; water monomer at 20℃; for 1h; Molecular sieve;	106.1 Step 1: (R)-2,2-Dimethyl-[1,3]dioxolane-4-carbaldehyde Sodium periodate (57.0 g, 270 mmol) was dissolved in hot water (115 mL) and silica (200 g, 60 220-440 mesh, particle size 35-75 μm) was added. The mixture was stirred vigorously until a free flowing powder was obtained. This was added to a solution of 1,2:5,6-bis-O-(1-methylethylidene)-D-mannitol (50 g, 190 mmol) in dichloromethane (1.0 L) and the reaction was stirred at room temperature for 1 hour. The resultant mixture was filtered through a pad of Na2SO4 and the solids washed thoroughly with dichloromethane. The combined organic extracts were evaporated in vacuo to yield 37.2 g (75%) of the title compound as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 9.73 (d, J=1.9 Hz, 1H), 4.38 (ddd, J=7.4, 4.7, 1.9 Hz, 1H), 4.18 (dd, J=8.8, 7.4 Hz, 1H), 4.10 (dd, J=8.8, 4.7 Hz, 1H), 1.49 (s, 3H), 1.43 (s, 3H).
73%	With sodium (meta)periodate; Sodium hydrogenocarbonate In dichloromethane at 0℃; for 2h; Inert atmosphere;
72%	With sodium (meta)periodate; Sodium hydrogenocarbonate In dichloromethane for 2h;
72%	With N-Bromosuccinimide; water monomer; potassium carbonate In acetonitrile var. of reagent, amount of catalyst, time;
70%	With sodium (meta)periodate; mesoporous silica In dichloromethane; water monomer at 20℃; for 0.166667h;
67%	With sodium (meta)periodate; water monomer; Sodium hydrogenocarbonate In dichloromethane at 30℃; for 4.33333h;
67%	With sodium (meta)periodate; Sodium hydrogenocarbonate for 1.5h; Inert atmosphere;
65%	With sodium (meta)periodate; Sodium hydrogenocarbonate In dichloromethane; water monomer
65%	With sodium (meta)periodate; Sodium hydrogenocarbonate In dichloromethane; water monomer at 20℃; for 2h;
63%	With sodium (meta)periodate; Sodium hydrogenocarbonate In dichloromethane
62%	With N-(tert-butyl)-N',N',N",N"-tetramethylguanidinium meta-iodoxybenzoate In dichloromethane at 40℃; for 2.5h;
61%	With sodium hydroxide; sodium (meta)periodate In water monomer for 1.5h; pH = 7.0;
59%	With lead tetraacetate
55%	With potassium metaperiodate; Sodium hydrogenocarbonate In dichloromethane at 25 - 30℃; for 2h;
55%	With sodium (meta)periodate In dichloromethane
52%	With N-Bromosuccinimide; triphenylbismuthine; potassium carbonate In water monomer; acetonitrile for 6h; Ambient temperature;
45%	With lead tetraacetate In ethyl acetate at 25℃; for 2.5h;
42%	With sodium (meta)periodate; Sodium hydrogenocarbonate In dichloromethane; water monomer at 22℃; for 1.5h;
40.1%	With sodium (meta)periodate; Potassium bicarbonate In tetrahydrofuran; water monomer at 18℃; for 2.5h; Cooling with ice;	2 Example 2 Was added to a 250 mL round bottom flaskNaIO4 (15 g, 70 mmol),Water (80 mL) was stirred, and KHCO3 (14 g, 140 mmol) was added in portions under ice-cooling,A solution of compound 12 (17.75 g, 70 mmol) in THF (55 mL) was added dropwise,30min drops finished, remove the ice bath,18 reaction 2h,Suction filtration turbid solution,Extracted three times with 20 mL of ethyl acetate,Merge several layers,Dried over anhydrous magnesium sulfate,Steamed out of the solvent to light yellowish oily liquid,Vacuum distillation65 ° C fractions,To give 7.135 g of a colorless oily liquid,The yield was 40.1%.
	With lead tetraacetate; benzene
	With lead tetraacetate In benzene for 1.5h; Ambient temperature;
60 mg	With A-26 resin (IO₄^(1-)) In water monomer at 20℃; for 2h;
	With sodium (meta)periodate; Sodium hydrogenocarbonate In water monomer for 1h; Ambient temperature;
	With sodium (meta)periodate; Sodium hydrogenocarbonate In water monomer at 0 - 5℃; for 1h;
	With sodium (meta)periodate; Sodium hydrogenocarbonate In water monomer for 1h; Ambient temperature;
	With sodium (meta)periodate; Sodium hydrogenocarbonate In water monomer for 1h; Ambient temperature;
	With lead tetraacetate In ethyl acetate Ambient temperature;
	With lead tetraacetate In tetrahydrofuran at 15℃; for 2h;
	With lead tetraacetate In toluene
	With lead tetraacetate In tetrahydrofuran 1.) 0-4 deg C, 30 min, 2.) RT, 30 min;
	With sodium (meta)periodate; Sodium hydrogenocarbonate In water monomer at 25℃; for 0.5h;
	With sodium (meta)periodate In water monomer at 5 - 10℃; for 1h;
	With sodium (meta)periodate In water monomer for 1.5h; Ambient temperature; pH 6-7;
	With sodium (meta)periodate; Sodium hydrogenocarbonate In methanol; water monomer at 22℃;
	With sodium (meta)periodate In methanol; water monomer for 0.5h; Ambient temperature;
	With phosphoric acid disodium salt; sodium periodate In water monomer for 0.25h; Ambient temperature;
	With lead tetraacetate
	With sodium (meta)periodate In water monomer for 0.5h;
	With lead tetraacetate In benzene for 0.333333h;
	With sodium (meta)periodate In water monomer for 0.166667h; ice-cooling;
	With lead tetraacetate In benzene Ambient temperature;
	With lead tetraacetate In tetrahydrofuran at 15℃; for 1.5h;
	With lead tetraacetate In tetrahydrofuran
	With sodium (meta)periodate In methanol; water monomer
	With lead tetraacetate In ethyl acetate for 1h; Ambient temperature;
	With sodium (meta)periodate; Sodium hydrogenocarbonate at 0℃; for 3h;
	With sodium (meta)periodate In tetrahydrofuran; water monomer for 1h;
	With lead tetraacetate In ethyl acetate
	With sodium (meta)periodate; Sodium hydrogenocarbonate In methanol; water monomer at 20℃; for 4h; ultrasonic irradiation;
	With sodium (meta)periodate; Sodium hydrogenocarbonate
	With sodium (meta)periodate; Sodium hydrogenocarbonate In dichloromethane at 20℃; for 5h;
	With sodium (meta)periodate; Sodium hydrogenocarbonate In water monomer at 20℃; for 1h;
	With sodium (meta)periodate
	With sodium (meta)periodate; Sodium hydrogenocarbonate In dichloromethane; water monomer for 2h;
	With sodium (meta)periodate; Sodium hydrogenocarbonate In methanol; water monomer at 0℃; for 1h;
	With sodium (meta)periodate; Sodium hydrogenocarbonate In dichloromethane; water monomer at 20℃; for 3h;
	With sodium (meta)periodate

[ CAS No. 1707-77-3 ] {[proInfo.proName]}

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[ 1707-77-3 ] Synthesis Path-Upstream 1~8

[ 1707-77-3 ] Synthesis Path-Downstream 1~88

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	With zinc(II) chloride In acetone for 2h; Ambient temperature;
	Multi-step reaction with 2 steps 1: 9 percent / 1,2-dimethoxy-ethane; methanol / 120 h / Heating 2: 70 percent / 1,2-dimethoxy-ethane / 48 h / Heating

Yield	Reaction Conditions	Operation in experiment
83%	With toluene-4-sulfonic acid In N,N-dimethyl-formamide at 0℃; for 2h;
65%	Stage #1: mannitol With calcium sulfate In N,N-dimethyl-formamide at 0℃; for 2h; Stage #2: 2-Methoxypropene With toluene-4-sulfonic acid In chloroform-d1 at 20℃; for 36h; Further stages.;
	With toluene-4-sulfonic acid In N,N-dimethyl-formamide for 1.5h;

Yield	Reaction Conditions	Operation in experiment
96%	With toluene-4-sulfonic acid
93%	With stannous chloride In 2-ethoxy-ethanol Heating;
84.3%	With pyridinium 4-toluenesulfonate In 1,4-dioxane at 50 - 82℃; for 2.5h;	7 Example 7 38 g of dioxane, 18.2 g of D-mannitol, and 23 g of 2,2-dimethoxypropane were placed in a dry clean reactor.After mixing with 0.1 g of p-toluenesulfonic acid pyridinium salt, the temperature was raised to 50 ° C, and the temperature was maintained at 50 ° C to 53 ° C.The temperature is kept for 1.5 hours, and then slowly heated to 78-82 ° C for the heat preservation reaction until the reaction liquid system is clarified.Transparent, clarified and then kept for 1h. After the end of the heat preservation, the temperature was slowly lowered to 20 ° C, and the recovery in Example 1 was directly added to the reaction liquid.The filtrate containing the mixture was stirred for 15 min, and then 60 g of petroleum ether was added for extraction by-products, stirred for 30 min, allowed to stand, layered, and collected.Phase; add ethyl acetate to the aqueous phase for extraction twice, each time with 75 g of ethyl acetate for extraction, combined two-phase extractionThe organic phase (ethyl acetate layer) was collected, and 5 g of anhydrous sodium sulfate was added to the organic phase for drying, and stirred for 15 min.The sodium sulfate was removed by filtration, the collected filtrate was concentrated to remove the solvent, and the concentrate was added to 120 g of n-hexane, and the mixture was stirred until the temperature was raised.Incubate at 43 ° C for 2 h, then cool to 16 ~ 18 ° C and stir for 2 h to precipitate the product, filter, filter cake to dry to obtain 22.1g whiteThe solid product diacetone-D-mannitol has a yield of 84.3% and a gas phase purity of 99.5%. As can be seen from the final product,The use of the recovered feedstock filtrate can also ensure the quality of the final product, still have a high purity quality, purity up toIt is over 99% and can maintain a good yield.

80%	With toluene-4-sulfonic acid In N,N-dimethyl-formamide
80%	With toluene-4-sulfonic acid In N,N-dimethyl-formamide
79%	With toluene-4-sulfonic acid In dimethyl sulfoxide at 20℃; for 6h;
78%	With stannous chloride In 1,2-dimethoxyethane for 4h; Reflux; Inert atmosphere;
76%	With perfluorosulfonic ionomer Aquivion-H In N,N-dimethyl-formamide at 20℃; for 16h; Inert atmosphere;	3. Experimental D-Mannitol (1 g, 5.49 mmol), Aquivion-H (133 mg, 0.153 mmol), 2,2dimethoxypropane (2.7 ml, 22.0 mmol) and 5 ml of dimethylformamidewere introduced into a round bottom flask under inert atmosphere. Thereaction mixture was vigorously stirred for 16 h at room temperature.Afterward the suspension was filtered to remove the catalyst and thefiltrate was concentrated under vacuum to obtain a white solid crudethat was triturated in cyclohexane (15 ml). 1 was recovered by filtrationas a white solid in 76% yield (1.09 g): mp = 120.3-121.6 C; [α]D25 =+2.6 (c 1, EtOH). 1H NMR (CDCl3) δ 4.19 (q, J = 6.2 Hz, 2H), 4.12 (dd, J= 8.4 Hz and 6.4 Hz, 2H), 3.97 (dd, J = 8.4 Hz and 5.6 Hz, 2H), 3.75 (t, J= 6.6 Hz, 2H), 2.59 (d, J = 6.6 Hz, 2H), 1.42 (s, 6H), 1.36 (s, 6H). 13CNMR (CDCl3) δ 109.4, 76.3, 71.2, 66.7, 26.7, 25.2. GC analysis of thediacetylated derivative showed >98% purity. The catalyst removedfrom the reaction mixture was rinsed with acetonitrile, dried undervacuum, and recycled for five times.
75%	With stannous chloride In 1,2-dimethoxyethane for 16h; Heating;
70%	With toluene-4-sulfonic acid In dimethyl sulfoxide for 16h; Ambient temperature;
70%	With toluene-4-sulfonic acid In N,N-dimethyl-formamide at 20℃; for 16h; Inert atmosphere;	(1S,2S)-1,2-bis((R)-2,2-dimethyl-1,3-dioxolan-4-yl)ethane-1,2-diol (S1) To a stirred solution of12(20 g, 109.88 mmol) in 80mL of dry DMF,pTSA (0.208 g, 0.108 mmol) was added and stirred for 16h under N2atmosphere at rt. Reaction mixture was quenched with 40 mL of sat. aq. NaHCO3solution, 300mL of ice cold water was added and extracted with (6x40 mL) of ethyl acetate, dried over Na2SO4, concentrated to get the crude which was purified by column chromatography with 45% ethyl acetate and hexanes to gave the pure ofS1(20.15 g, 70%).Molecular Formula: C12H22O6Rf= 0.1(50% ethyl acetate/hexanes)LRMS: (ES+)m/z= 285.4 [M+Na]+1H-NMR (CD3OD, 400 MHz) δ ppm4.12-3.89 (m, 4H), 3.87-3.79 (m, 2H), 3.62 (dd,J =6.56, 8.34 Hz, 2H), 3.47 (m, 2H),1.27 (d,J =3.45 Hz, 6H),1.22 (d,J =5.89 Hz, 6H);13C NMR (CD3OD, 100 MHz)δ ppm109.2, 108.4, 79.2, 76.2, 75.5, 71.4, 70.5, 66.0, 27.6, 27.1, 26.6, 25.4
70.9%	Stage #1: mannitol With stannous chloride In acetone for 1h; Large scale; Stage #2: 2,2-dimethoxy-propane In acetone at 20 - 40℃; for 5h; Large scale;	1 1) Into the reactor, first add 500L acetone, add batchwise 100 kg D-mannitol and 1 kg stannous chloride. Stir for 1 hour. Control temperature at 20 °C-25 °C add 120 kg 2,2-dimethoxypropane, Heat to 35-40 °C react for 5 hours. The said technological, concentrated under reduced pressure to remove acetone, residue by adding dichloromethane stir. In another reactor by adding saturated sodium carbonate aqueous solution about 500L, the above-mentioned residue batch is added to saturated sodium carbonate aqueous solution, control system PH=8 - 9. canada finishes, stir at room temperature 30 minutes, liquid, takes organically phase, organic uses purified water washing. The organic phase is dried with anhydrous sodium sulfate, concentrated under reduced pressure to job to a kind of white solid D-mannitol diacetonide 102 kg, yield: 70.9%.
67%	In dimethyl sulfoxide Ambient temperature;
61%	With toluene-4-sulfonic acid In dimethyl sulfoxide at 20℃; for 1h;
60%	With stannous chloride In 1,2-dimethoxyethane
58%	With stannous chloride In 1,2-dimethoxyethane at 74℃; for 1.5h;
58%	With stannous chloride In 1,2-dimethoxyethane
57%	With toluene-4-sulfonic acid In water monomer; N,N-dimethyl-formamide at 20℃;
55%	With toluene-4-sulfonic acid In dimethyl sulfoxide for 48h; Ambient temperature;
54%	With stannous chloride In various solvent(s)
54%	With 1,2-dimethoxyethane; stannous chloride
53%	With magnesium(II) chloride In acetone for 7h; Heating;
53%	With stannous chloride In 1,2-dimethoxyethane Reflux; Inert atmosphere;
52%	With toluene-4-sulfonic acid In 1,4-dioxane Reflux; Inert atmosphere;
50%	With stannous chloride In 1,2-dimethylethanediol for 0.5h; Heating / reflux;	1.1 Preparation 1: Preparation of2,2-difluoro-3-hydroxy-3-(2,2-dimethyl-[l,3]dioxoran-4-yl)propionate (compound of formula (V)); Step 1: Preparation of l,2-bis-(2,2-dimethyl-l,3-dioxoran-4-yl)-ethane-l,2-diol; 100 g of d-mannitol was mixed with 160 ml of 2,2-dimethoxypropane, 240 ml of 1,2-dimethylethanediol and 0.1 g of anhydrous SnCk, the mixture was heated until a homogeneous solution was obtained, and refluxed for 30 min, and 0.2 ml of pyridine was added thereto. The reaction mixture was cooled to room temperature, and distilled under areduced pressure to remove the solvent. 700 ml of methylchloride was added to the residue and refluxed for 1 hour. The resulting mixture was filtered through 10 g of cellite at room temperature, and the filtrate was distilled under a reduced pressure to remove the solvent. The residue was recrystallized from 1 L of hexane, filtered, and dried to obtain 72.4 g (yield 50%) of the title compound as a white solid.NMR (300 MHz, CDC13): 1.30(s, 6H), 1.36(s, 6H), 2.52(d, 2H), 3.67(t, 2H), 3.91(m, 2H), 4.04-4.14(m,4H)Melting point (m.p.): 119~121°C
47.3%	With toluene-4-sulfonic acid In tetrahydrofuran; DMF (N,N-dimethyl-formamide) at 20 - 45℃; for 20h;	31.A [0469] N-[(R-)2,3-Dihydroxy-propoxy]-2-(4-ethyl-2-fluoro-phenylamino)-3,4-difluoro-benzamide; [0470] Step A: Preparation of 1,2:5,6-di-O-isopropylidene-D-mannitol [0471] To a stirring suspension of D-Mannitol (1.82 g, 10.0 mmol) in tetrahydrofuran (21 mL) and dimethylformamide (9 mL) was added p-toluenesulfonic acid monohydrate (0.02 g, 0.1 mmol,) at ambient temperature, followed by 2,2-dimethoxypropane (2.8 mL, 0.023 mol). The reaction mixture was stirred for 18 hours at room temperature, then additional 2,2-dimethoxypropane (0.3 mL, 2.4 mmol) was added. The suspension was heated to 40° C. to 45° C., and stirred for 2 hours. Sodium bicarbonate (1.8 g, 0.016 mol) was added to neutralize the acid and the mixture was stirred for 30 minutes. The excess Na2CO3 was filtered and washed with tetrahydrofuran (5 mL). The filtrate was concentrated. To the remaining light yellow oil was added toluene (15 mL) and the mixture was stirred at 3° C. to 5° C. until a light-yellow gelatinous solid formed. The solid was filtered and washed with hexane (2×5 mL). The product was dried in a vacuum oven for 18 hours to give 1,2:5,6-di-O-isopropylidene-D-mannitol (1.24 g, 47.3%) as an off-white solid, mp 110-113° C.
47.3%	With toluene-4-sulfonic acid In tetrahydrofuran; DMF (N,N-dimethyl-formamide); water monomer at 20 - 45℃; for 20h;	1.A [0154] To a stirring suspension of D-Mannitol (1.82 g, 10.0 mmol) in tetrahydrofuran (21 mL) and dimethylformamide (9 mL) was added p-toluenesulfonic acid monohydrate (0.02 g, 0.1 mmol,) at ambient temperature, followed by 2,2-dimethoxypropane (2.8 mL, 0.023 mol). The reaction mixture was stirred for 18 hours at room temperature, then additional 2,2-dimethoxypropane (0.3 mL, 2.4 mmol) was added. The suspension was heated to 40° C. to 45° C., and stirred for 2 hours. Sodium bicarbonate (1.8 g, 0.016 mol) was added to neutralize the acid and the mixture was stirred for 30 minutes. The excess Na2CO3 was filtered and washed with tetrahydrofuran (5 mL). The filtrate was concentrated. To the remaining light yellow oil was added toluene (15 mL) and the mixture was stirred at 3° C. to 5° C. until a light-yellow gelatinous solid formed. The solid was filtered and washed with hexane (2×5 mL). The product was dried in a vacuum oven for 18 hours to give 1,2:5,6-di-O-isopropylidene-D-mannitol (1.24 g, 47.3%) as an off-white solid, mp 110-113° C.
46%	With toluene-4-sulfonic acid In dimethyl sulfoxide at 20℃; for 16h;
38%	With 1,2-dimethoxyethane; stannous chloride Reflux;
36%	With stannous chloride In 1,2-dimethoxyethane for 3h; Reflux;
35%	With stannous chloride In 1,2-dimethoxyethane Reflux;
	With stannous chloride
40.3 g	With toluene-4-sulfonic acid In dimethyl sulfoxide at 28℃; for 24h;
	Stage #1: mannitol; 2,2-dimethoxy-propane With stannous chloride In 1,2-dimethoxyethane for 1h; Heating; Stage #2: With pyridine In 1,2-dimethoxyethane Further stages.;
	With pyridinium 4-toluenesulfonate In dimethyl sulfoxide at 20℃;
	In dimethyl sulfoxide at 20 - 25℃; for 18h;	1.a EXAMPLE-I 0 Preparation of enantiomeric mixture of D-Glyceraldehvde ketonide; a) charge D-mannitol (100 g), 2,2-dimethoxy propane (152 g) and p-toluenesulphonic acid (1.0 g) to dimethyl sulphoxide (200 ml). The mixture is stirred for 2 h at a temperature of about 200C to 250C to dissolve completely the reactants. The mixture is maintained between 200C to 250C for further 16 h. Check TLC of the reaction mixture for completion, quench the 5 reaction mixture at a temperature of O0C to 5 C by adding aqueous sodium bicarbonate solution (15 g in 600 ml H2O). Raise the temperature to 200C to 250C, extract with ethyl acetate (800 ml), wash ethyl acetate layer with water, dry over anhydrous sodium sulphate, filter and concentrate to one tenth of its volume and add n-hexane to crystallize the title compound (70 g).
	With stannous chloride
	Stage #1: mannitol; 2,2-dimethoxy-propane In 1,2-dimethoxyethane for 0.833333 - 1.5h; Stage #2: With pyridine In 1,2-dimethoxyethane for 0.166667h;	1; A To a 5L four neck round bottom flask fitted with Thermometer pocket, condenser with CaCI2 guard tube and overhead stirrer were added 600 ml of 1 ,2- dimethyoxy ethane, 250gm of D-mannitol and 400 ml of 2,2-dimethoxy propane. The mixture was stirred at room temperatures and 375 mg of anhydrous stannous chloride was added to the reaction mixture. The slurry was heated to reflux for approximately 50 to 90 min until mixture becomes clear. The solution was cooled below reflux temperature & pyridine (0.5ml) was added to the reaction mixture and the same was stirred for 10 minutes. The solution was concentrated below 40 to 45°C to give thick solid mass. The mixture was allowed to cool to room temperature (25°C). Methylene dichloride (500 ml) was added to it and mixture was stirred at room temperature for 30 minutes. Hexane (2. 5L) was added to this mixture and cooled to 0-100C and stirred for more 30 min and filtered off. The white solid was dried in vacuum at 35-400C for 4 hrs. 200gm white solid obtained has GC purity 99%.

Yield	Reaction Conditions	Operation in experiment
95%	With zinc(II) chloride at 23℃; Inert atmosphere;
88%	With zinc(II) chloride at 20℃; for 24h;
83%	Stage #1: acetone With zinc(II) chloride at 20℃; for 0.5h; Cooling with ice; Stage #2: mannitol at 20℃; for 17h; Stage #3: With potassium carbonate In water for 0.5h;	1 Example 1 A 500 mL round bottom flask was charged with 240 mL of acetone, cooled in an ice bath,Add anhydrous zinc chloride (35 g,260 mmol) was stirred for 30 min,Remove the ice bath,Add D-mannitol(23 g, 130 mmol),After 17 h reaction at room temperature,Get white turbid liquid.A solution of potassium carbonate (35 g of potassium carbonate dissolved in 35 mL of water) was added,Stirring 30min after filtration,The filtrate was washed with CH2Cl2 (50 mL) to give a colorless filtrate. The filtrate was added dropwise with ammonia to adjust pH = 7.5,There is a white precipitate generated,Filtered to obtain a colorless liquid,The filtrate was subjected to rotary evaporation to obtain an oily substance,Plus CH2Cl2 (50mL),Part of the precipitation dissolved,Filter the filtrate,Take the CH2Cl2 layer,Dried over anhydrous magnesium sulfate,Steamed white solid,Recrystallization was carried out using a mixed solvent (1:10) of 400 mL of ethyl acetate and petroleum ether,To give 27.6 g of a white solid in 83.0% yield,

80%	Stage #1: mannitol; acetone With zinc(II) chloride at 20℃; for 4h; Inert atmosphere; Stage #2: With potassium carbonate In diethyl ether; water at 20℃; for 1.5h; Inert atmosphere;
78%	With zinc(II) chloride at 20℃; for 16h;
78%	With zinc(II) chloride at 20℃; for 24h;
78%	With zinc(II) chloride at 20℃; for 24h;
77%	Stage #1: mannitol In dimethyl sulfoxide at 0℃; for 0.5h; Stage #2: acetone With toluene-4-sulfonic acid In dimethyl sulfoxide at 0 - 20℃; for 15.5h;	4.2 General procedure for the synthesis of product 2 In a round-bottom flask, 10.0g of D-mannitol (54.9mmol) was added, followed by addition of 30mL of dimethylsulfoxide (DMSO). The reaction mixture was kept under magnetic stirring at 0°C for 30min. Next, 0.2g of p-toluenesulfonic acid (2mol%) and 20mL of acetone were added and the reaction kept at 0°C for 30min and room temperature for 15h. Next, the crude reaction mixture was diluted in ethyl acetate (30.0mL) and a liquid-liquid extraction employing a 5% m/v of an aqueous solution of NaHCO3 (three aliquots of 100.0mL) carried out. The organic phase was then dried under reduced pressure and further purification by column chromatography (silica gel) employing isocratic eluent 1:1 ethyl acetate/hexane was carried out. 4.2.1 (1S,2S)-1,2-bis((R)-2,2-dimethyl-1,3-dioxolan-4-yl)ethane-1,2-diol (2) (0027) White solid, 11.1g, yield: 77%. m.p.: 118.0-120.0°C. [α]25D [α]D25 +2.4 (c 1.0, EtOH). IR (ATR) ν (cm-1): 3389, 2978, 2942, 2887, 2849, 1628, 1445, 1402, 1366, 1162, 1076, 1003, 918.1H NMR (500MHz, CDCl3) δ: 4.17 (q, J 6.3Hz, 2H), 4.11 (dd, J 8.6Hz, J 6.4Hz, 2H), 3.97 (dd, J 8.6Hz, J 5.6Hz, 2H), 3.74 (t, J 6.6Hz, 2H), 2.69 (d, J 6.5Hz, 2H), 1.41 (s, 6H), 1.35 (s, 6H). 13C {1H} NMR (125MHz, CDCl3) δ: 109.5, 76.4, 71.3, 66.9, 26.9, 25.3.
75%	With zinc(II) chloride
60%	With zinc(II) chloride
60%	With potassium carbonate; zinc(II) chloride In water cooling;
60%	With zinc(II) chloride Inert atmosphere;
55%	With zinc(II) chloride at 20℃;
55%	With zinc(II) chloride In acetone at 20℃; for 3h;
55%	With zinc(II) chloride at 20℃; for 30h;
55%	at 20℃; for 18 - 19h;	1.1F IF. Preparation of l,2:5,6-Di-0-isopropylidene-D-mannitol: To a solution of 60 grams of zinc chloride in 30OmL of acetone was added 10 grams of finely powdered D-mannitol. The mixture was stirred vigorously at 20°C until clear solution (2-3 hours) and was allowed to stand for further 16 hours. The reaction mixture was then poured into a solution of 70 grams of potassium carbonate in 70 mL of water and 300 mL of ether. The product was filtered and 100 mL of 1 :1 acetone- ether solution was used to wash the filtrate. The combined filtrates were evaporated to dryness on a rotary evaporator. The dry residue was successively extracted with five 250-mL portions of boiling light petroleum (b.p. 60-800C) and the combined filtrates cooled to give the product, 7.9 grams (55%), having m.p.l 19°C.
55%	Stage #1: mannitol; acetone With zinc(II) chloride at 20℃; for 18 - 19h; Stage #2: With potassium carbonate In diethyl ether; water	1F To a solution of 6Og of zinc chloride in 300ml of acetone was added 1Og of finely powdered D-mannitol. The mixture was stirred vigorously at 20°C until clear solution (2- 3 hours) and was allowed to stand for further 16 hours. The reaction mixture was then poured into a solution of 7Og of potassium carbonate in 70ml of water and 300ml of ether. The product was filtered and 100ml of 1:1 acetone-ether solution was used to wash the filtrate. The combined filtrates was evaporated to dryness on a rotary evaporator. The dry residue was successively extracted with five 250-ml portions of boiling light petroleum (b.p. 60-80°C) and the combined filtrates cooled to give the ρroduct,7.9g (55%), having m.p.l 19°C.
53%	With zinc(II) chloride
51%	With zinc(II) chloride
41%	With zinc(II) chloride at 0 - 22℃; for 15h;
35%	With zinc(II) chloride at 20℃; for 12h;
	With zinc(II) chloride 1) 3 d, 2) 2 h, room temperature; Yield given. Multistep reaction;
	With zinc(II) chloride Yield given. Multistep reaction;
	With zinc(II) chloride at 20℃;
	With zinc(II) chloride
	With zinc(II) chloride
	With zinc(II) chloride at 20℃; for 3h;

Yield	Reaction Conditions	Operation in experiment
93%	With dmap In dichloromethane at 0℃; for 1h;
93%	With dmap In tetrachloromethane; dichloromethane at 0℃; for 1h;
90%	With dmap In dichloromethane

Yield	Reaction Conditions	Operation in experiment
97%	With tris(dibenzylideneacetone)dipalladium ⁽⁰⁾; 1,4-di(diphenylphosphino)-butane In tetrahydrofuran at 65℃; for 12h;
97%	With tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; 1,4-di(diphenylphosphino)-butane In tetrahydrofuran at 65℃; for 4h;
97%	With 1,4-di(diphenylphosphino)-butane In tetrahydrofuran at 65℃; for 4h;

Yield	Reaction Conditions	Operation in experiment
13.2%	With dmap; dicyclohexyl-carbodiimide In dichloromethane for 11h; Ambient temperature;
	With dmap; dicyclohexyl-carbodiimide In tetrahydrofuran Ambient temperature;

Yield	Reaction Conditions	Operation in experiment
96%	With sodium hydroxide; tetrabutylammomium bromide In tetrahydrofuran at 40℃; for 20h;
96%	With tetra-(n-butyl)ammonium iodide; sodium hydride
95%	With tetra-(n-butyl)ammonium iodide; sodium hydride In tetrahydrofuran at 0 - 20℃;

95%	With tetra-(n-butyl)ammonium iodide; sodium hydride In tetrahydrofuran at 0 - 20℃;
93%	With tetrabutylammomium bromide; sodium hydride In tetrahydrofuran at 20℃; for 24h; Inert atmosphere;
93%	With tetra-(n-butyl)ammonium iodide; sodium hydride In tetrahydrofuran
90%	With tetra-(n-butyl)ammonium iodide; sodium hydroxide In tetrahydrofuran; water at 50 - 60℃; for 12h;
87%	With tetrabutylammomium bromide; sodium hydroxide In tetrahydrofuran; water at 20 - 40℃; for 23h;
84%	Stage #1: 1,2:5,6-di-O-isopropylidene-D-mannitol With sodium hydride In tetrahydrofuran at 0℃; for 2h; Stage #2: benzyl bromide With tetra-(n-butyl)ammonium iodide In tetrahydrofuran at 20℃; for 6h; Further stages.;
84%	Stage #1: 1,2:5,6-di-O-isopropylidene-D-mannitol With sodium hydride In tetrahydrofuran at 0℃; for 2h; Stage #2: benzyl bromide With tetra-(n-butyl)ammonium iodide In tetrahydrofuran at 20℃; for 6h; Further stages.;
61%	With sodium hydroxide; tetra(n-butyl)ammonium hydrogensulfate at 40℃; for 22h;
	With sodium hydride 1) DMF, 1.5 h; 2) DMF, 5 h; Yield given. Multistep reaction;
	With sodium hydride In N,N-dimethyl-formamide
	With potassium hydroxide In dimethyl sulfoxide at 20℃;
	Stage #1: benzyl bromide; 1,2:5,6-di-O-isopropylidene-D-mannitol With potassium hydride In N,N-dimethyl-formamide at 20℃; Stage #2: With acetic acid In methanol at 20℃;	2.VII VII. Protection of hydroxyl groups in diisopropylidene- D- mannitol (5) with benzylic groups 2g (1.4ml) of benzyl bromide (13) in 1ml of DMF (dry) was added dropwise to a mixture of lg (3.8mmol) di isopropylidene D-mannitol in 15ml of DMF (dry) and 0.8g of KH 35% in oil at room temperature. The reaction was stirred overnight. The mixture was then acidified with IN HC1. The product was extracted with ethyl acetate. The organic solution was washed with water and brine, dried over MgSC , and filtered. MS analysis was not clear, so 3ml of CH3OH (dry) and 0.15ml of acetyl chloride were added, and the reaction mixture was stirred at room temperature overnight. TLC (hexane -ethyl acetate 7:3) was performed. Several new spots were observed. Diethyl ether was added, and the precipitated salts were filtered out. The organic phase was washed with water, dried over MgSC , and filtered, and the solvent was removed under reduced pressure. The product (14 in Scheme 7) (MS m/z = [M+18]+= 460.07) was separated by column chromatography using 90g of silica gel for flash and hexane -ethyl acetate 20% 11 and then hexane -ethyl acetate 40% .

Yield	Reaction Conditions	Operation in experiment
92%	With pyridine; dmap at 22℃;
91%	With triethylamine In dichloromethane for 6h; Inert atmosphere;
90%	In pyridine for 3h; Ambient temperature;

Yield	Reaction Conditions	Operation in experiment
1: 17% 2: 61%	With triethylamine In dichloromethane at 0℃; for 2h;
	With triethylamine In dichloromethane for 3h;	General synthesis of cyclic oxalate with oxalyl chloride: General procedure: A mixture of trans-1,2-cyclohexanediol (1 × 10-2 mol, 1.16 g) and oxalyl chloride (1 × 10-2 mol, 1.18 mL) in pyridine (2 ×10-2 mol, 1.54 mL) and CH2Cl2 (20 mL) solution was stirred for 3 h. After 3 h, the reaction mixture was added CH2Cl2 (50 mL), water (30 mL) and 0.01 N HCl (20 mL). The combined organic layers were dried over separated, anhydrous Na2SO4 filtered and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel eluted with ethylacetate and hexane, to provide trans-1,2-cyclohexanediol 1,2-oxalate (67 %) and 1-O-carboxycarbonyl trans-1,2-cyclohexanediol (25 %).

Yield	Reaction Conditions	Operation in experiment
98%	In trifluoroacetic acid for 72h; Ambient temperature;
89%	In tetrahydrofuran for 14h; Heating;
85%	In tetrahydrofuran for 7h; Heating;

Yield	Reaction Conditions	Operation in experiment
88%	Stage #1: 1,2:5,6-di-O-isopropylidene-D-mannitol With <i>N</i>,<i>N</i>-dimethyl-formamide dimethyl acetal at 55℃; for 3h; Stage #2: With acetic anhydride at 130℃; for 3h;
81%	Stage #1: 1,2:5,6-di-O-isopropylidene-D-mannitol With <i>N</i>,<i>N</i>-dimethyl-formamide dimethyl acetal In dichloromethane at 20℃; for 20h; Stage #2: With methyl iodide In toluene for 1h; Heating; Further stages.;
74%	With 1H-imidazole; 2,4,6-triiodoimidazole; triphenylphosphine In toluene for 1.5h; Heating; other diol, other temperature; stereospecific conversion of acyclic vicinal diols into olefins;

74%	With 1H-imidazole; 2,4,5-triiodoimidazole; triphenylphosphine In toluene for 1.5h; Heating;
	With acetic anhydride; <i>N</i>,<i>N</i>-dimethyl-formamide dimethyl acetal Multistep reaction;
	Multi-step reaction with 2 steps 1.1: NaH; imidazole / tetrahydrofuran / 0.5 h / 20 °C 1.2: 90 percent / tetrahydrofuran / 0.5 h / 20 °C 2.1: 86 percent / (Bu₄N)2S₂O₈; HCO₂Na; Na₂CO₃ / dimethylformamide / 1 h / 65 °C
	Multi-step reaction with 2 steps 1: 83 percent / tetrahydrofuran / 16 h / 65 °C 2: 94 percent / 1,3-dimethyl-2-phenyl-1,3,2-diazaphospholidine / 24 h / 40 °C
	Multi-step reaction with 2 steps 1: 89 percent / NaH / tetrahydrofuran 2: 84 percent / tris(trimethylsilyl)silane; azobisizobutyronitrile / benzene / 3 h / 80 °C
	Multi-step reaction with 3 steps 1: 9 percent / imidazole, 2,4,5-triiodoimidazole, triphenylphosphine / toluene / 80 °C 2: 83 percent / Na, MeOH / 1.5 h / Heating 3: 65 percent / imidazole, 2,4,5-triiodoimidazole, triphenylphosphine / toluene / Heating
	Multi-step reaction with 2 steps 1: 93 percent / 4-dimethylaminopyridine / CH₂Cl₂; CCl₄ / 1 h / 0 °C 2: 88 percent / 1,3-dimethyl-2-phenyl-1,3,2-diazaphospholidine / 20 h / 40 °C

Yield	Reaction Conditions	Operation in experiment
86.4%	Stage #1: 1,2:5,6-di-O-isopropylidene-D-mannitol With lead(IV) acetate In ethyl acetate for 0.583333h; Stage #2: With sodium tetrahydroborate In ethanol Further stages.;
72%	Stage #1: 1,2:5,6-di-O-isopropylidene-D-mannitol With lead(IV) acetate In tetrahydrofuran at 0 - 20℃; for 1h; Stage #2: With sodium hydroxide; sodium tetrahydroborate In tetrahydrofuran at 10 - 28℃; for 2h;
60%	Stage #1: 1,2:5,6-di-O-isopropylidene-D-mannitol With sodium periodate; sodium hydrogencarbonate In water at 0 - 20℃; for 2h; Stage #2: With sodium tetrahydroborate In water at 0 - 20℃;	31.B [0472] Step B: Preparation of (S)-(+)-(2,2-dimethyl-[1,3]dioxolan-4-yl)-methanol [0473] To a solution of the product of Example 31, Step A, 1,2:5,6-di-O-isopropylidene-D-mannitol (50 g, 0.191 mol), in water (700 mL), was added solid sodium bicarbonate (20 g). The resultant solution was stirred until all the solid dissolved, and then cooled in an ice-water bath. Solid sodium periodate (81.5 g, 0.381 mol) was slowly added to the solution portionwise. Gas evolution observed. The white mixture was stirred at ambient temperature for 2 hours. Solid sodium chloride (30 g) was added, and the mixture was stirred for 15 minutes. The white solid was filtered. The filtrate was cooled in an ice-water bath. Solid sodium borohydride was added slowly. Gas bubbles evolved. The mixture was warmed to ambient temperature, and stirred overnight. The milky mixture turned to a clear solution. The aqueous solution was extracted with dichloromethane (3×). The organic solution was washed with brine, and dried over magnesium sulfate. The solvent was removed in vacuo to give (S)-(+)-(2,2-dimethyl-[1,3]dioxolan-4-yl)-methanol as a colorless oil, which was dried under high vacuum at ambient temperature overnight, 34.82 g (60%); MS (APCI+)=133 (M++1).

60%	With sodium periodate; sodium hydrogencarbonate In water at 0 - 20℃; for 2h;	1.B [0156] To a solution of the product of Preparation 1, Step A, 1,2:5,6-di-O-isopropylidene-D-mannitol (50 g, 0.191 mol), in water (700 mL), was added solid sodium bicarbonate (20 g). The resultant solution was stirred until all the solid dissolved, and then cooled in an ice-water bath. Solid sodium periodate (81.5 g, 0.381 mol) was slowly added to the solution portionwise. Gas evolution observed. The white mixture was stirred at ambient temperature for 2 hours. Solid sodium chloride (30 g) was added, and the mixture was stirred for 15 minutes. The white solid was filtered. The filtrate was cooled in an ice-water bath. Solid sodium borohydride was added slowly. Gas bubble evolved. The mixture was warmed to ambient temperature, and stirred overnight. The milky mixture turned to a clear solution. The aqueous solution was extracted with dichloromethane (3×). The organic solution was washed with brine, and dried over magnesium sulfate. The solvent was removed in vacuo to give (S)-(+)-(2,2-dimethyl-[1,3]dioxolan-4-yl)-methanol as a colorless oil, which was dried under high vacuum at ambient temperature overnight, 34.82 g (60%); MS (APCI+)=133 (M++1).
45%
	With lead(IV) acetate; sodium hydroxide; sodium tetrahydroborate 1.) THF, a) 10 deg C, 30 min, b) RT, 1 h, 2.) a) 10 deg C, 30 min, b) RT, 90 min; Yield given. Multistep reaction;
	With sodium periodate
	With hydrogenchloride; sodium hydroxide; sodium tetrahydroborate; potassium metaperiodate 1.) water/THF, rt., pH=7-8; 2.) water/THF, rt., 2 h, pH=7-8; Yield given. Multistep reaction;
	With sodium tetrahydroborate; sodium periodate Yield given. Multistep reaction;
	Yield given. Multistep reaction;
	With sodium tetrahydroborate; sodium periodate; disodium hydrogenphosphate; sodium methylate 1.) methanol, RT, 42 h, 2.) 1 h; Yield given. Multistep reaction;
	With Amberlite A₂₇ borohydride form; Amberlite A₂₇ periodate form In methanol; water for 2h;
	With lead(IV) acetate; lithium aluminium tetrahydride Yield given. Multistep reaction;
	With lithium hydroxide; sodium tetrahydroborate; sodium periodate 1.) methanol, 20 degC, 15 min; 2.) 20 min, ice cooling; Yield given. Multistep reaction;
	With BH₄^- resin; IO₄^- resin Multistep reaction;
	Multi-step reaction with 2 steps 1: NaIO₃, Na₂HPO₄*2H₂O / H₂O / 0.25 h / Ambient temperature 2: NaBH₄ / H₂O / 3 h / Ambient temperature
	Multi-step reaction with 2 steps 1: NaIO₄ / H₂O / 1.5 h / Ambient temperature; pH 6-7 2: NaBH₄ / 1 h / 15 - 20 °C
	Multi-step reaction with 2 steps 1: NaIO₄, NaHCO₃ / methanol; H₂O / 1 h / 0 °C 2: NaBH₄ / 0 - 10 °C
	Multi-step reaction with 2 steps 1: NaIO₄, NaHCO₃ / H₂O / 0.5 h / 25 °C 2: NaBH₄ / H₂O / 1 h / 25 °C
	Multi-step reaction with 2 steps 1: Pb(OAc)4 / ethyl acetate / Ambient temperature 2: NaBH₄
	Multi-step reaction with 2 steps 1: NaIO₄ / H₂O / 0.17 h / ice-cooling 2: NaBH₄ / H₂O / 1.4 h / 0 °C
	Multi-step reaction with 2 steps 1: 52 percent / triphenylbismuth, N-bromosuccinimide, K₂CO₃ / H₂O; acetonitrile / 6 h / Ambient temperature 2: 1.) triphenylbismuth, N-bromosuccinimide, K₂CO₃, 2.) NaBH₄ / 1.) aqueous acetonitrile, room temperature, 1.25 h, 2.) methanol, 40 deg C, 4 h
	Multi-step reaction with 2 steps 1: 72 percent / NaHCO₃, NaIO₄ / CH₂Cl₂ / 2 h 2: NaBH₄
	Multi-step reaction with 2 steps 1: lead (IV)-acetate; benzene 2: Raney nickel; aqueous ethyl acetate / Hydrogenation
	Multi-step reaction with 2 steps 1.1: sodium hydrogencarbonate / water / 0.17 h / 0 °C 1.2: 1 h / 0 °C 2.1: sodium tetrahydroborate / ethanol; water / 2 h / 0 °C

Yield	Reaction Conditions	Operation in experiment
89%	With sodium hydroxide; p-toluenesulfonyl chloride In dichloromethane for 0.5h; Ambient temperature;
	With sodium hydride; p-toluenesulfonyl chloride 1.) THF, 0 deg C, 10 min, 2.) THF, 30 min; Yield given. Multistep reaction;
	Multi-step reaction with 2 steps 1: pyridine 2: chloroform; sodium methylate; methanol

Yield	Reaction Conditions	Operation in experiment
87%	With dmap; triethylamine In tetrahydrofuran for 8h; Ambient temperature;
	With triethylamine In diethyl ether

Yield	Reaction Conditions	Operation in experiment
1: 15% 2: 54%	With pyridine; dmap Ambient temperature;
54%	With dmap In pyridine at 0℃; Yields of byproduct given;
	With dmap In pyridine at 0℃; Yield given. Yields of byproduct given;

Yield	Reaction Conditions	Operation in experiment
74%	Stage #1: 1,2:5,6-di-O-isopropylidene-D-mannitol With lead(IV) acetate In tetrahydrofuran at 0℃; for 0.166667h; Stage #2: methyl 2-cyanoacetate With acetic anhydride In tetrahydrofuran for 24h; Heating; Further stages.;
	With lead(IV) acetate; acetic anhydride 1.) THF, 0 deg C, 5 min, 2.) THF, reflux, 18 h; Yield given. Multistep reaction;

	With sodium periodate; sodium hydrogencarbonate In dichloromethane; water at 20 - 25℃; Large scale;	2 2) Into ther eactor was added 375L dichloromethane, add under stirring 100 kg D-mannitol diacetonide, obtain colorless clear liquid, add 98 kg sodium periodate. Control temperature at 20 °C-25 °C slowly add dropwise 30L saturated aqueous solution of sodium bicarbonate, dropping complete then stir reaction for 1-2 hours. The said technological, centrifugal, solid and dichloromethane is used for washing to no product, the filtrate with anhydrous sodium sulfate stirring drying, centrifugal removing desiccant, product solution, directly used for the next step reaction, is named as the reaction liquid 1.
	With sodium periodate In dichloromethane

Yield	Reaction Conditions	Operation in experiment
81%	With 1H-imidazole In N,N-dimethyl-formamide at 40℃; Yields of byproduct given;
	With 1H-imidazole In N,N-dimethyl-formamide at 40℃; Yield given. Yields of byproduct given;

Yield	Reaction Conditions	Operation in experiment
63%	With 1H-imidazole In dichloromethane at 0℃; Yields of byproduct given;
	With 1H-imidazole In dichloromethane at 0℃; Yield given. Yields of byproduct given;

Yield	Reaction Conditions	Operation in experiment
79.2%	With sodium hydroxide; tetrabutyl-ammonium chloride; water In toluene for 0.5h; Heating;
	With sodium hydroxide; tetrabutyl-ammonium chloride In toluene

Yield	Reaction Conditions	Operation in experiment
65%	With sodium hydride In dimethyl sulfoxide at 50℃; for 3h;
38%	Stage #1: 1,2:5,6-di-O-isopropylidene-D-mannitol With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0℃; for 0.5h; Inert atmosphere; Stage #2: p-methoxybenzyl chloride In N,N-dimethyl-formamide; mineral oil at 0 - 20℃; Inert atmosphere;
	With sodium hydride In N,N-dimethyl-formamide

Yield	Reaction Conditions	Operation in experiment
100%	With sodium periodate; silica gel In dichloromethane at 20℃; for 20h;
88%	With sodium periodate; silica gel In diethyl ether; water at 20℃;

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: NaIO₄; NaHCO₃ / H₂O / 1 h / 20 °C 2: 20.0 g / K₂CO₃ / H₂O / 20 h / 20 °C 3: hydrogen / Pd(OH)2/C / methanol / 2 h
	Multi-step reaction with 2 steps 1.1: NaIO₄ / aq. NaHCO₃ / 1 h / 20 °C 1.2: 96 percent / aq. K₂CO₃ / 17 h / 20 °C 2.1: 94 percent / H₂ / Pd/C / ethanol / 0.75 h / 20 °C
	Multi-step reaction with 3 steps 1: NaIO₄, NaHCO₃ / H₂O / 1 h / Ambient temperature 2: 86 percent / K₂CO₃ / H₂O / 20 h / Ambient temperature 3: 95 percent / H₂ / 10percent Pd-C / ethanol / 10 h / Ambient temperature

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: NaIO₄; NaHCO₃ / H₂O / 1 h / 20 °C 2: 20.0 g / K₂CO₃ / H₂O / 20 h / 20 °C
	Multi-step reaction with 2 steps 1: oxidating reagent
	Multi-step reaction with 2 steps 1: 76 percent / Pb(OAc)4, K₂CO₃ 2: methanol / 1 h / 0 °C