* 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.
With hydrogenchloride In water at 20 - 30℃; for 7 h;
in room temperature,Hydrochloric acid (21 mL, 21 mmol, 1 M) was added(3aS, 3bR, 7aS, 8aS) -2,2,5,5-tetramethyltetrahydro-3aaH- [1,3] dioxolo [4 ', 5': 4,5] Furo [3,2-d] [1,3] dioxane 1b (110 g, 477.72 mmol)In aqueous solution (450 mL),The resulting reaction was stirred at room temperature for 7 hours.The mixture was adjusted to pH 7 with saturated aqueous sodium bicarbonate solution,And concentrated under reduced pressure. The resulting residue was dissolved in ethyl acetate (600 mL)The insoluble matter was removed by filtration,The filter cake was washed with ethyl acetate (100 mL x 3), the filtrates were combined, concentrated under reduced pressure,To give the title compound 1c as a yellow oil (70.0 g, 77.0percent).
Reference:
[1] RSC Advances, 2016, vol. 6, # 46, p. 39758 - 39761
[2] Tetrahedron, 1981, vol. 37, p. 1685 - 1690
[3] Patent: CN106892948, 2017, A, . Location in patent: Paragraph 0188; 0189; 0190; 0191
[4] Helvetica Chimica Acta, 1938, vol. 21, p. 263,267
[5] Nucleosides, Nucleotides and Nucleic Acids, 2001, vol. 20, # 4-7, p. 703 - 706
[6] Tetrahedron, 1988, vol. 44, # 15, p. 4721 - 4736
[7] Collection of Czechoslovak Chemical Communications, 2006, vol. 71, # 7, p. 1063 - 1087
[8] Patent: US2009/30198, 2009, A1, . Location in patent: Page/Page column 7
[9] Patent: US2010/16422, 2010, A1, . Location in patent: Page/Page column 4
[10] Collection of Czechoslovak Chemical Communications, 2011, vol. 76, # 5, p. 503 - 536
[11] Patent: WO2012/140596, 2012, A1, . Location in patent: Page/Page column 54-55
in room temperature,A solution of magnesium sulfate (160 g, 1.33 mol) and concentrated sulfuric acid (9.9 mL, 190 mmol)(2S, 3R, 4S) -2,3,4,5-tetrahydroxyvaler 1a (99.0 g, 659 mmol)In acetone (1.2 L)The resulting reaction was stirred for 12 hours.The reaction mixture was suction filtered,Washed with acetone (300 mL x 2)Combined filtrate,With 25percent ammonia to adjust the pH to 7,Solid precipitated, filtered again and washed with acetone (150 mL x 2). The filtrate was combined, concentrated under reduced pressure,The title compound Ib was obtained as a yellow oil (128.0 g, 84.3percent).
Reference:
[1] Patent: CN106892948, 2017, A, . Location in patent: Paragraph 0183; 0185; 0186; 0187
[2] Nucleosides, Nucleotides and Nucleic Acids, 2001, vol. 20, # 4-7, p. 703 - 706
[3] Collection of Czechoslovak Chemical Communications, 2006, vol. 71, # 7, p. 1063 - 1087
[4] Patent: WO2012/140596, 2012, A1, . Location in patent: Page/Page column 53-55
4
[ 18467-77-1 ]
[ 131156-47-3 ]
Reference:
[1] Chemical Communications, 2007, # 48, p. 5244 - 5246
[2] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1990, # 4, p. 945 - 954
5
[ 58-86-6 ]
[ 67-64-1 ]
[ 131156-47-3 ]
Yield
Reaction Conditions
Operation in experiment
85%
at 40℃; for 3 h; Green chemistry
General procedure: To asuspension of the substrate (2 mmol) in dry acetone (10 mL),CAT600 (100 mg) was added. Then the mixture was stirred at 40 °C till the TLC (n-hexane-EtOAc 2:1) showed the completion of the reaction. The catalyst was separated by filtration, washed with acetone, dried, and reused for a consecutive run under the same reaction conditions. The filtrate was condensed to dry in vacuum, and the residue was dissolved in CH2Cl2 (10 mL) and washed with 3 × 5 mL brine.The organic layer was dried over anhydrous Na2SO4, filtered and evaporated to afford the crude product. Then the desired pure product was obtained by recrystallization from n-hexane. While, the silica gel column chromatography was used if the product existed in the liquid form.
Reference:
[1] Bulletin of the Korean Chemical Society, 2014, vol. 35, # 7, p. 2165 - 2168
With copper(II) sulfate; at 20 - 25℃; for 16.0h;Industry scale;Product distribution / selectivity;
L-xylose 1 (1000 g, 6.66 moles, 1 eq), acetone (10 L), copper sulfate (1.33 kg, 8.3 moles, 1.25 eq), and Amberlyst0 15 resin (1000g) were combined in a 22 L round bottom flask fitted with a mechanical stirrer, temperature probe, and nitrogen inlet/outlet. The reaction was stirred under nitrogen at room temperature for 16 hours. TLC (100% ethyl acetate, visualization with phosphomolybdic acid (PMA) ) showed no starting material (Rf-0. 05). 750 g of solid sodium carbonate was added and stirred for 30 minutes. The solution was filtered through Celite0 (diatomite, World Minerals Inc., Santa Barbara, CA) to remove solids. The filtrate was concentrated to an oil under vacuum to yield 1.4 kg of a clear oil. 1H NMR confirmed absence of L-xylose 1. The oil was then dissolved in 7 L of a 4: 1 methanol/water solution. While stirring, 1.4 kg of Amberlyst0 15 resin was added at room temperature. The solution was stirred at room temperature until TLC (100% ethyl acetate, visualization with PMA) showed the absence of di-protected xylose 2 (Rf-0. 75). The solution was filtered and the filtrate was brought to pH 8 with solid sodium bicarbonate (approximately 20 g). The solvent was removed under vacuum at 50% to yield 1160 g of a light oil. The oil was triturated with 10 L of a 3: 2 dichloromethane/ethyl acetate solution and dried over sodium sulfate. The dried solution was then filtered through Celite0 and concentrated under vacuum to yield 1055 g (83%) of 3. 1H NMR and TLC confirmed structure.; Preparation of Acetal 3 A reaction vessel was charged with L-xylose 1 (1.0 wt, 1.0 mol eq) and acetone (7.9 wt, 10.0 vol). The resultant slurry was stirred vigorously and anhydrous copper sulfate (1.33 wt) was added while maintaining the reaction temperature below 25C. Amberlyst0 15 resin (1.00 wt) was then added while maintaining the reaction temperature below 25C. The resulting mixture was stirred vigorously at 20-25C until the reaction to form 2 was deemed complete by 1H NMR (<1 mol % L-xylose 1 remaining, typically about 16 hours). The mixture was then filtered through Celite (X3 and the filtrate transferred via a 1 jim filter to a second vessel. The filter cake was washed with acetone (2 x 1. 58 wt, 2 x 2.0 vol) and the combined filtrates were transferred to a second vessel containing sodium carbonate (0.5 wt). The resulting mixture was stirred vigorously for 30-40 minutes, after which it was verified that the supernatant liquid in water had pH > 7. The mixture was then concentrated by vacuum distillation at up to 30C to ca 5 vol. Industrial methylated spirits (IMS, 2.02 wt, 2.5 vol) was then charged to the vessel and the resulting mixture was concentrated to ca 5 vol under vacuum at 25-30C. A further portion of IMS (2.02 wt, 2.5 vol) was charged to the vessel and the resulting mixture was distilled under vacuum at 25-35C to ca 5 vol. The IMS charge and distillation was repeated once more. 1H NMR was used to verify that the sample contained less than 1 mol % of acetone with respect to ethanol. The mixture was then filtered and the filter cake washed with IMS (1.62 wt, 2.0 vol). The combined filtrate and wash were heated to 25-30C, and a 1.2 M HC1 solution (0.34 vol) was added while maintaining the reaction temperature at 25-30C. The pH at this point was <1. The reaction mixture was stirred until deprotection to form compound 3 was deemed complete by 1H NMR (>94 mol% product 3, typically about 4 hours). The resulting mixture was transferred to a separate vessel, which contained a slurry of sodium bicarbonate (1.0 wt) in IMS (1.61 wt, 2.0 vol), while maintaining the temperature at 20-30C. The resulting mixture was stirred for 30-40 minutes, after which it was verified that the supernatant liquid in water had pH > 7. The mixture was concentrated by vacuum distillation at up to 35C to ca 4 vol. Toluene (4.31 wt, 5.0 vol) was then charged to the vessel, and the resulting mixture was concentrated to ca 4 vol in vacuo at 25-35C. A further portion of toluene (4.31 wt, 5.0 vol) was charged to the vessel, and the vessel contents were concentrated to ca 4 vol total in vacuo at 25- 35C. 1H NMR was used to verify that the sample contained <1 mol% ethanol (IMS) with respect to toluene. Tertiary butyl methyl ether (TBME) (2.96 wt, 4.0 vol) was then charged to the vessel, and 1H NMR analysis was performed to verify that the toluene/TBME molar ratio was 1: 1. The resultant mixture was stirred for 30-40 minutes before being filtered, and the filter cake was washed with TBME (1.48 wt, 2.0 vol).
With Amberlyst 15 resin; In methanol; water; at 20℃;Industry scale;Product distribution / selectivity;
L-xylose 1 (1000 g, 6.66 moles, 1 eq), acetone (10 L), copper sulfate (1.33 kg, 8.3 moles, 1.25 eq), and Amberlyst0 15 resin (1000g) were combined in a 22 L round bottom flask fitted with a mechanical stirrer, temperature probe, and nitrogen inlet/outlet. The reaction was stirred under nitrogen at room temperature for 16 hours. TLC (100% ethyl acetate, visualization with phosphomolybdic acid (PMA) ) showed no starting material (Rf-0. 05). 750 g of solid sodium carbonate was added and stirred for 30 minutes. The solution was filtered through Celite0 (diatomite, World Minerals Inc., Santa Barbara, CA) to remove solids. The filtrate was concentrated to an oil under vacuum to yield 1.4 kg of a clear oil. 1H NMR confirmed absence of L-xylose 1. The oil was then dissolved in 7 L of a 4: 1 methanol/water solution. While stirring, 1.4 kg of Amberlyst0 15 resin was added at room temperature. The solution was stirred at room temperature until TLC (100% ethyl acetate, visualization with PMA) showed the absence of di-protected xylose 2 (Rf-0. 75). The solution was filtered and the filtrate was brought to pH 8 with solid sodium bicarbonate (approximately 20 g). The solvent was removed under vacuum at 50% to yield 1160 g of a light oil. The oil was triturated with 10 L of a 3: 2 dichloromethane/ethyl acetate solution and dried over sodium sulfate. The dried solution was then filtered through Celite0 and concentrated under vacuum to yield 1055 g (83%) of 3. 1H NMR and TLC confirmed structure.
With hydrogenchloride; In IMS; water; at 25 - 30℃;pH <= 1;Industry scale;Product distribution / selectivity;
Preparation of Acetal 3 A reaction vessel was charged with L-xylose 1 (1.0 wt, 1.0 mol eq) and acetone (7.9 wt, 10.0 vol). The resultant slurry was stirred vigorously and anhydrous copper sulfate (1.33 wt) was added while maintaining the reaction temperature below 25C. Amberlyst0 15 resin (1.00 wt) was then added while maintaining the reaction temperature below 25C. The resulting mixture was stirred vigorously at 20-25C until the reaction to form 2 was deemed complete by 1H NMR (<1 mol % L-xylose 1 remaining, typically about 16 hours). The mixture was then filtered through Celite (X3 and the filtrate transferred via a 1 jim filter to a second vessel. The filter cake was washed with acetone (2 x 1. 58 wt, 2 x 2.0 vol) and the combined filtrates were transferred to a second vessel containing sodium carbonate (0.5 wt). The resulting mixture was stirred vigorously for 30-40 minutes, after which it was verified that the supernatant liquid in water had pH > 7. The mixture was then concentrated by vacuum distillation at up to 30C to ca 5 vol. Industrial methylated spirits (IMS, 2.02 wt, 2.5 vol) was then charged to the vessel and the resulting mixture was concentrated to ca 5 vol under vacuum at 25-30C. A further portion of IMS (2.02 wt, 2.5 vol) was charged to the vessel and the resulting mixture was distilled under vacuum at 25-35C to ca 5 vol. The IMS charge and distillation was repeated once more. 1H NMR was used to verify that the sample contained less than 1 mol % of acetone with respect to ethanol. The mixture was then filtered and the filter cake washed with IMS (1.62 wt, 2.0 vol). The combined filtrate and wash were heated to 25-30C, and a 1.2 M HC1 solution (0.34 vol) was added while maintaining the reaction temperature at 25-30C. The pH at this point was <1. The reaction mixture was stirred until deprotection to form compound 3 was deemed complete by 1H NMR (>94 mol% product 3, typically about 4 hours). The resulting mixture was transferred to a separate vessel, which contained a slurry of sodium bicarbonate (1.0 wt) in IMS (1.61 wt, 2.0 vol), while maintaining the temperature at 20-30C. The resulting mixture was stirred for 30-40 minutes, after which it was verified that the supernatant liquid in water had pH > 7. The mixture was concentrated by vacuum distillation at up to 35C to ca 4 vol. Toluene (4.31 wt, 5.0 vol) was then charged to the vessel, and the resulting mixture was concentrated to ca 4 vol in vacuo at 25-35C. A further portion of toluene (4.31 wt, 5.0 vol) was charged to the vessel, and the vessel contents were concentrated to ca 4 vol total in vacuo at 25- 35C. 1H NMR was used to verify that the sample contained <1 mol% ethanol (IMS) with respect to toluene. Tertiary butyl methyl ether (TBME) (2.96 wt, 4.0 vol) was then charged to the vessel, and 1H NMR analysis was performed to verify that the toluene/TBME molar ratio was 1: 1. The resultant mixture was stirred for 30-40 minutes before being filtered, and the filter cake was washed with TBME (1.48 wt, 2.0 vol).
With sulfonated polystyrene cation exchange resin CAT600; at 40℃; for 3.0h;Green chemistry;
General procedure: To asuspension of the substrate (2 mmol) in dry acetone (10 mL),CAT600 (100 mg) was added. Then the mixture was stirred at 40 C till the TLC (n-hexane-EtOAc 2:1) showed the completion of the reaction. The catalyst was separated by filtration, washed with acetone, dried, and reused for a consecutive run under the same reaction conditions. The filtrate was condensed to dry in vacuum, and the residue was dissolved in CH2Cl2 (10 mL) and washed with 3 × 5 mL brine.The organic layer was dried over anhydrous Na2SO4, filtered and evaporated to afford the crude product. Then the desired pure product was obtained by recrystallization from n-hexane. While, the silica gel column chromatography was used if the product existed in the liquid form.
[(3aS,5R,6S,6aS)-6-hydroxy-2,2-dimethyl-3a,5,6,6a-tetrahydrofuro[2,3-d][1,3]dioxolan-5-yl]-[3-[(4-benzyloxyphenyl)methyl]-4-chlorophenyl]methanone[ No CAS ]
(3aS,5S,6R,6aS)-5-[(S)-[3-[(4-benzyloxyphenyl)methyl]-4-chlorophenyl]-hydroxymethyl]-2,2-dimethyl-3a,5,6,6a-tetrahydrofuro[2,3-d][1,3]dioxolan-6-ol[ No CAS ]
(2S,3R,4R,5S,6R)-2-[4-chloro-3-[[4-[[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methoxy]phenyl]methyl]phenyl]-6-methylthiotetrahydropyran-3,4,5-triol[ No CAS ]
[(3aS,5R,6S,6aS)-6-hydroxy-2,2-dimethyl-3a,5,6,6a-tetrahydrofuro[2,3-d][1,3]dioxolan-5-yl]-[3-[(4-benzyloxy-3-fluorophenyl)methyl]-4-chloro-phenyl]methanone[ No CAS ]
(2S,3R,4R,5S,6R)-2-[4-chloro-3-[[4-[[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methoxy]phenyl]methyl]phenyl]-6-methylthiotetrahydropyran-3,4,5-triol[ No CAS ]
With sulfuric acid; copper(II) sulfate; at 20℃; for 24.0h;
Add D-xylose (15.0 g, 0.1 mol) to a 500 mL round bottom flaskAnhydrous copper sulfate (34.4 g, 0.216 mol) was added thereto, and 150 mL of acetone and 3 mL of 98% concentrated sulfuric acid were further added thereto, and the reaction was stirred at room temperature. The mixture is yellow-green and cloudy.When standing, the upper layer is a pale yellow liquid and the lower layer is a light blue solid.As the reaction proceeded, the turbid solution gradually turned tan. Reaction for 24 h,The resulting mixture was filtered under reduced pressure and the cake was light blue. The cake was washed with acetone and the filtrate was combined.A yellow transparent liquid is obtained. Concentrated aqueous ammonia was added dropwise to the filtrate to pH-7.0, and sulfuric acid was neutralized.A white floc precipitate (NH4)2S04 was formed. Filter (NH4) 2S04, filter cake washed with acetone,A colorless liquid is obtained. The filtrates were combined and dried in a single-necked flask using a rotary evaporator (temperature ? 50 C).Concentrated to a yellow brown syrupy substance.
With hydrogenchloride; In water; at 20℃; for 1.5h;
The diacetone fork D-xylose obtained in the previous step was added with 100 mL of 0.1 mol·L-1 dilute hydrochloric acid.The product is insoluble.After stirring at room temperature, the solution gradually dissolved and reacted for 1.5 h. TLC tracking,Use a CH2Cl2 developer. After the reaction, solid sodium hydrogencarbonate was added to adjust to pH 7. 2 to 7.5.The mixture was poured into a separatory funnel and about 30 mL of diethyl ether was added. The layers were shaken and the organic layer was bright yellow.Liquid separation. Wash twice more until the organic phase is colorless.It was spin-dried (temperature ? 50 C) with a rotary evaporator and concentrated to give a colorless syrupy material.