ethyl (3R)-3-hydroxybutanoate

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred, room temperature solution of ethyl (R)-3-hydroxybutanoate (5.00 g, 37.8 mmol) and tert-butyldimethylsilyl chloride (6.85 g, 45.5 mmol) in DMF (90 mL) was added imidazole (3.87 g, 56.9 mmol). This reaction mixture was stirred at room temperature for 18 hours. The reaction mixture was partitioned between hexane (300 mL) and water (100 mL). The organic layer was washed with water (2×100 mL) then dried (MgSO4) and filtered. The filtrate was concentrated under reduced pressure to give the title compound. The reaction mixture was partitioned between hexane (300 mL) and water (100 mL) The organic layer was washed with water (2×100 mL) then dried (MgSO4) filtered The filtrate was concentrated under reduced pressure

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Geotrichum candidum (ATCC 34614) was cultured according to the method of Buisson and Azerad (Tet. Lett. 27, 2631-2634 (1986), herein incorporated by reference) in one liter of a medium of glucose (30 grams), KH2PO4 (1 gram), K2HPO4 (2 grams), corn steep liquor (10 grams) MgSO4.7H20 (0.5 gram), NaNO3 (2 grams), FeSO4.7H20 (0.02 gram), and KC1(0.5 gram) with rotary shaking at 25° C. Two grams of ethyl acetoacetate was dissolved in 2 ml of 95% ethanol, the resulting solution was added to the culture, and shaking was resumed. The reaction was followed by TLC (staining with anisaldehyde) to monitor the consumption of starting material and the production of product alcohol. After approximately 48 hours the reaction was judged complete, and the reaction was terminated by removing from the shaker and adding 20-30 grams of Celite. The resulting suspension was suction filtered through a pad of Celite and the clear yellow filtrate was extracted with ethyl acetate (4×200 ml). The extracts were combined, dried over MgSO4, filtered, and rotary evaporated to leave 1.4 grams of (R)-ethyl 3-hydroxybutyrate as a yellow oil. the resulting solution was added to the culture shaking the consumption of starting material the reaction was terminated by removing from the shaker adding 20-30 grams of Celite filtered through a pad of Celite the clear yellow filtrate was extracted with ethyl acetate (4×200 ml) dried over MgSO4 filtered rotary evaporated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: tert-Butylchlorodimethylsilane (547 g, 3.63 mol) was added to a stirred solution of (R)-ethyl 3-hydroxybutanoate (400 g, 3.03 mol) in DCM (800 mL) under nitrogen at 0° C. Imidazole (412 g, 6.05 mol) was added portion wise over 20 min to the reaction mixture during which time the mixture became a thick white slurry. Additional DCM (175 mL) was added and the mixture was allowed to warm to room temperature and stirred for 16 h. The white solid was removed by filtration, rinsed with DCM (500 mL), partitioned between water (1 L) and DCM (500 mL), and the aqueous layer was further extracted with additional DCM (500 mL). The filtrate was combined with the organic layers and washed with water (500 mL) and brine, dried over MgSO4 and filtered. The product was concentrated and dried under high vacuum to yield (R)-ethyl 3-(tert-butyldimethylsilyloxy)butanoate (777.5 g), containing unidentified impurities. The analytical data of the crude product complied with data reported in the literature. The material was used without additional purification. The white solid was removed by filtration rinsed with DCM (500 mL) partitioned between water (1 L) and DCM (500 mL) the aqueous layer was further extracted with additional DCM (500 mL) washed with water (500 mL) and brine dried over MgSO4 filtered The product was concentrated dried under high vacuum

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: tert-Butylchlorodimethylsilane (547 g, 3.63 mol) was added to a stirred solution of (R)-ethyl 3-hydroxybutanoate (400 g, 3.03 mol) in DCM (800 mL) under nitrogen at 0° C. Imidazole (412 g, 6.05 mol) was added portion wise over 20 min to the reaction mixture during which time the mixture became a thick white slurry. Additional DCM (175 mL) was added and the mixture was allowed to warm to room temperature and stirred for 16 h. The white solid was removed by filtration, rinsed with DCM (500 mL), partitioned between water (1 L) and DCM (500 mL), and the aqueous layer was further extracted with additional DCM (500 mL). The filtrate was combined with the organic layers and washed with water (500 mL) and brine, dried over MgSO4 and filtered. The product was concentrated and dried under high vacuum to yield (R)-ethyl 3-(tert-butyldimethylsilyloxy)butanoate (777.5 g), containing unidentified impurities. The analytical data of the crude product complied with data reported in the literature. The material was used without additional purification. The white solid was removed by filtration rinsed with DCM (500 mL) partitioned between water (1 L) and DCM (500 mL) the aqueous layer was further extracted with additional DCM (500 mL) washed with water (500 mL) and brine dried over MgSO4 filtered The product was concentrated dried under high vacuum

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred, room temperature solution of ethyl (R)-3-hydroxybutanoate (5.00 g, 37.8 mmol) and tert-butyldimethylsilyl chloride (6.85 g, 45.5 mmol) in DMF (90 mL) was added imidazole (3.87 g, 56.9 mmol). This reaction mixture was stirred at room temperature for 18 hours. The reaction mixture was partitioned between hexane (300 mL) and water (100 mL). The organic layer was washed with water (2×100 mL) then dried (MgSO4) and filtered. The filtrate was concentrated under reduced pressure to give the title compound. The reaction mixture was partitioned between hexane (300 mL) and water (100 mL) The organic layer was washed with water (2×100 mL) then dried (MgSO4) filtered The filtrate was concentrated under reduced pressure

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 30 g of ethyl acetoacetate, 5 ml of degassed ethanol and 0.9 ml of 1 N HCl are introduced in succession into a Schlenk vessel filled with argon. This solution and the catalyst solution from Example C1 are then transferred in succession by means of a steel capillary into a 50 ml steel autoclave filled with argon. The s/c (substrate/catalyst) ratio is 75 000. The autoclave is closed and a pressure of 50 bar is set using 4 flushing cycles (pressurization with 20 bar of hydrogen). The autoclave is then heated to 80° C., and after 30 minutes the reaction pressure is set to 80 bar. The autoclave is stirred for 19 hours. The heating is subsequently switched off and the autoclave is cooled to room temperature. After depressurization, a reddish reaction solution is isolated. The conversion is >98% (determined by means of GC and 1H-NMR). Removal of the solvent on a rotary evaporator gives a quantitative yield of ethyl (R)-3-hydroxybutyrate having an enantiomeric purity of 97.1% ee. (determined by means of GC after reaction with trifluoroacetic anhydride; column: Lipodex E, 50 m). filled with argon filled with argon The autoclave is closed after 30 minutes the reaction pressure the autoclave is cooled to room temperature After depressurization, a reddish reaction solution is isolated Removal of the solvent on a rotary evaporator

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a liquid mixture comprising 15 ml of water, 15 ml of ethanol and sodium hydroxide was dissolved 4.0 of ethyl (R)-β-hydroxybutanoate, and the solution was refluxed under heating, cooled and passed through an ion exchange resin (Amberlite1/2 IR-120B). The solvent was removed under a reduced pressure, 10 ml of anhydrous pyridine and 3 ml of anhydrous acetic acid were added to the residue, and the mixture was stirred at room temperature overnight. Dilute hydrochloric acid was added to the reaction liquid to adjust the pH value to 1, and the reaction liquid was saturated with sodium chloride and extracted with chloroform. The extract was washed with a saturated aqueous sodium chloride solution and dehydrated on magnesium sulfate. Then, chloroform was removed under a reduced pressure to obtain 3.6 g of the intended compound having [α]24 of -5.7°. the solution was refluxed under heating cooled The solvent was removed under a reduced pressure, 10 ml of anhydrous pyridine and 3 ml of anhydrous acetic acid were added to the residue Dilute hydrochloric acid was added to the reaction liquid the reaction liquid extracted with chloroform The extract was washed with a saturated aqueous sodium chloride solution Then, chloroform was removed under a reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a liquid mixture comprising 15 ml of water, 15 ml of ethanol and sodium hydroxide was dissolved 4.0 of ethyl (R)-β-hydroxybutanoate, and the solution was refluxed under heating, cooled and passed through an ion exchange resin (Amberlite1/2 IR-120B). The solvent was removed under a reduced pressure, 10 ml of anhydrous pyridine and 3 ml of anhydrous acetic acid were added to the residue, and the mixture was stirred at room temperature overnight. Dilute hydrochloric acid was added to the reaction liquid to adjust the pH value to 1, and the reaction liquid was saturated with sodium chloride and extracted with chloroform. The extract was washed with a saturated aqueous sodium chloride solution and dehydrated on magnesium sulfate. Then, chloroform was removed under a reduced pressure to obtain 3.6 g of the intended compound having [α]24 of -5.7°. the solution was refluxed under heating cooled The solvent was removed under a reduced pressure, 10 ml of anhydrous pyridine and 3 ml of anhydrous acetic acid were added to the residue Dilute hydrochloric acid was added to the reaction liquid the reaction liquid extracted with chloroform The extract was washed with a saturated aqueous sodium chloride solution Then, chloroform was removed under a reduced pressure

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 0.077 mol (10.0 g) of ethyl(R)-3-hydroxybutyrate is dissolved in 90 ml of dimethylformamide and 0.151 mol (10.3 g) of imidazole is added. The mixture is cooled to 0° C. under protective gas in an ice bath and 0.083 mol (16.05 g) of triisopropylsilyl chloride is added dropwise over 5 min. The mixture is stirred at room temperature for a further 5 hours, hydrolyzed with water, the product is extracted with tert-butyl methyl ether, and the organic phase is dried using Na2SO4 and concentrated under reduced pressure on a rotary evaporator. the product is extracted with tert-butyl methyl ether the organic phase is dried concentrated under reduced pressure on a rotary evaporator

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 0.077 mol (10.0 g) of ethyl(R)-3-hydroxybutyrate is dissolved in 90 ml of dimethylformamide and 0.151 mol (10.3 g) of imidazole is added. The mixture is cooled to 0° C. under protective gas in an ice bath and 0.083 mol (16.05 g) of triisopropylsilyl chloride is added dropwise over 5 min. The mixture is stirred at room temperature for a further 5 hours, hydrolyzed with water, the product is extracted with tert-butyl methyl ether, and the organic phase is dried using Na2SO4 and concentrated under reduced pressure on a rotary evaporator. the product is extracted with tert-butyl methyl ether the organic phase is dried concentrated under reduced pressure on a rotary evaporator

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Ethyl acetoacetate (7.5 g) and dry methanol (25 mL) were mixed and deoxygenated with flowing nitrogen for five minutes. The catalyst [(R)—Ru(BINAP)Cl2]2NEt3 (0.1 mol %) was added along with 2N HCl (0.1 mol %). The mixture was transferred to a standard Parr reactor apparatus and flushed by evacuating and refilling with hydrogen several times. The apparatus was heated at 50° C. with stirring under 100 psi of hydrogen for 16 h. After completion of reaction (monitored by TLC) the reaction was cooled and concentrated under reduced pressure. The residue was subjected to column chromatographic purification with petroleum ether/ethyl acetate (9:1 v/v) to get pure (R)-alcohol 43 as a colorless liquid. deoxygenated with flowing nitrogen for five minutes The catalyst [(R)—Ru(BINAP)Cl2]2NEt3 (0.1 mol %) was added along with 2N HCl (0.1 mol %) flushed by evacuating After completion of reaction (monitored by TLC) the reaction was cooled concentrated under reduced pressure The residue was subjected to column chromatographic purification with petroleum ether/ethyl acetate (9:1 v/v)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: tert-Butylchlorodimethylsilane (547 g, 3.63 mol) was added to a stirred solution of (R)-ethyl 3-hydroxybutanoate (400 g, 3.03 mol) in DCM (800 mL) under nitrogen at 0° C. Imidazole (412 g, 6.05 mol) was added portion wise over 20 min to the reaction mixture during which time the mixture became a thick white slurry. Additional DCM (175 mL) was added and the mixture was allowed to warm to room temperature and stirred for 16 h. The white solid was removed by filtration, rinsed with DCM (500 mL), partitioned between water (1 L) and DCM (500 mL), and the aqueous layer was further extracted with additional DCM (500 mL). The filtrate was combined with the organic layers and washed with water (500 mL) and brine, dried over MgSO4 and filtered. The product was concentrated and dried under high vacuum to yield (R)-ethyl 3-(tert-butyldimethylsilyloxy)butanoate (777.5 g), containing unidentified impurities. The analytical data of the crude product complied with data reported in the literature. The material was used without additional purification. The white solid was removed by filtration rinsed with DCM (500 mL) partitioned between water (1 L) and DCM (500 mL) the aqueous layer was further extracted with additional DCM (500 mL) washed with water (500 mL) and brine dried over MgSO4 filtered The product was concentrated dried under high vacuum