4-溴乙酰乙酸乙酯

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a mechanically-stirred solution of ethyl acetoacetate (59 mL, 463 mmol) in ether (75 mL) was added bromine (23.5 mL, 912 mmol) while the reaction temperature was maintained below 23° C. using an ice-water bath. The yellow-orange solution was stirred for 5 hours with cooling and then was stirred overnight at ambient temperature. Ice (60 g) was added and the reaction mixture was extracted with ether. The organic phase was washed twice with aqueous NaHCO3 saturated with NaCl and once with brine. The ether solution was stirred for 1 day over CaCl2 and then was filtered through celite. The filter cake was rinsed with dichloromethane. The filtrate was concentrated in vacuo to give ethyl 4-bromoacetoacetate (71.5 g) which was stored in the dark and stabilized with BaCO3 (300 mg). was maintained below 23° C. with cooling was stirred overnight at ambient temperature the reaction mixture was extracted with ether The organic phase was washed twice with aqueous NaHCO3 saturated with NaCl and once with brine The ether solution was stirred for 1 day over CaCl2 was filtered through celite The filter cake was rinsed with dichloromethane The filtrate was concentrated in vacuo

反应条件: temp:30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The recombinant E. coli HB101(pNTS1G) obtained in Example 10 was inoculated in 100 ml of a 2×YT medium sterilized in a 500 ml Sakaguchi flask, and cultured with agitation at 37° C. for 13 hours. Glucose, 1.3 g, 3.2 mg of NADP, and then 1 g of ethyl 4-bromoacetoacetate were added to 50 ml of the resultant culture. The culture was stirred at 30° C. while being adjusted at pH 6.5 with a 5 M sodium hydroxide solution to allow for reaction for 18 hours. After the reaction, the reaction solution was subjected to extraction using ethyl acetate, the solvent was removed under decompression, and the concentrate was purified by silica gel chromatography, to obtain 900 mg of ethyl (S)-4-bromo-3-hydroxybutyrate. The optical purity of the ethyl (S)-4-bromo-3-hydroxybutyrate was analyzed as follows and found to be 100% e.e. That is, the sample was converted to a carbamate using phenyl isocyanate under the presence of pyridine and the optical purity of the carbamate was measured by an HPLC method. 1H-NMR(CDC13)δ(ppm): 1.38(3H,t), 2.75(2H,m), 3.28(1H,br), 3.51(2H,m), 4.18(3H,q), 4.25(1H,m); Column: Chiralcel OJ (0.46×25 cm) manufactured by Daicel Chemical Industries, Co., Ltd.; Column temperature: 25° C.; Eluent: n-hexane/2-propanol of 9/1: Flow rate: 0.8 ml/min.; Detection: 254 nm; Elution time: 24.2 minutes for (S), 27.8 minutes for (R). coli HB101(pNTS1G) obtained in Example 10 to allow for reaction for 18 hours After the reaction the reaction solution was subjected to extraction the solvent was removed under decompression the concentrate was purified by silica gel chromatography

反应条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of sodium nitrite (12.4 g.) in water (150 ml.) was dropwise added with stirring at 5° to 7° C. to a solution of ethyl 4-bromoacetoacetate (30 g.) in acetic acid (200 ml.) and the mixture was stirred for 2 hours at 10° C. Water (200 ml.) was added to the reaction mixture and the resultant mixture was extracted with ether (500 ml.). The extract was washed twice with water (200 ml.) and with a sodium chloride aqueous solution (200 ml.) and dried over magnesium sulfate. The solvent was distilled off under reduced pressure to give yellowish brown crystals of ethyl 2-hydroxyimino-4-bromoacetoacetate (a mixture of syn and anti isomers) (32.6 g.). the resultant mixture was extracted with ether (500 ml.) The extract was washed twice with water (200 ml.) and with a sodium chloride aqueous solution (200 ml.) dried over magnesium sulfate The solvent was distilled off under reduced pressure

反应条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of sodium nitrite (12.4 g.) in water (150 ml.) was dropwise added with stirring at 5° to 7° C. to a solution of ethyl 4-bromoacetoacetate (30 g.) in acetic acid (200 ml.) and the mixture was stirred for 2 hours at 10° C. Water (200 ml.) was added to the reaction mixture and the resultant mixture was extracted with ether (500 ml.). The extract was washed twice with water (200 ml.) and with a sodium chloride aqueous solution (200 ml.) and dried over magnesium sulfate. The solvent was distilled off under reduced pressure to give yellowish brown crystals of ethyl 2-hydroxyimino-4-bromoacetoacetate (a mixture of syn and anti isomers) (32.6 g.). the resultant mixture was extracted with ether (500 ml.) The extract was washed twice with water (200 ml.) and with a sodium chloride aqueous solution (200 ml.) dried over magnesium sulfate The solvent was distilled off under reduced pressure

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Ethyl γ-bromoacetoacetate [2.62 g, 0.9-1.0 mole, described by A. Burger and G. E. Ullyot, J. Org. Chem., 12, 346 (1947)]is added in one portion to a suspension of thiobenzamide [117.5 g, 0.857 mole, described by A. Silberg et al., Ber., 94, 2887 (1961)] in ethanol. The clear solution is refluxed on a steam bath for 2 hr, cooled and slowly added with stirring to ether (3500 ml). The white crystalline precipitate is collected, washed with ether and partitioned between water and ether. Sodium bicarbonate is added in portions until the mixture is alkaline. The mixture is extracted with ether, the ether solution is washed with saturated sodium chloride solution, dried, and evaporated to give ethyl 2-phenylthiazole-4-acetate (VII; R1 = H, R9 = CH2CH3), γmaxCHCl3 1725 cm-1. The clear solution is refluxed on a steam bath for 2 hr cooled slowly added The white crystalline precipitate is collected washed with ether partitioned between water and ether Sodium bicarbonate is added in portions until the mixture The mixture is extracted with ether the ether solution is washed with saturated sodium chloride solution dried evaporated

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Ethyl γ-bromoacetoacetate [2.62 g, 0.9-1.0 mole, described by A. Burger and G. E. Ullyot, J. Org. Chem., 12, 346 (1947)]is added in one portion to a suspension of thiobenzamide [117.5 g, 0.857 mole, described by A. Silberg et al., Ber., 94, 2887 (1961)] in ethanol. The clear solution is refluxed on a steam bath for 2 hr, cooled and slowly added with stirring to ether (3500 ml). The white crystalline precipitate is collected, washed with ether and partitioned between water and ether. Sodium bicarbonate is added in portions until the mixture is alkaline. The mixture is extracted with ether, the ether solution is washed with saturated sodium chloride solution, dried, and evaporated to give ethyl 2-phenylthiazole-4-acetate (VII; R1 = H, R9 = CH2CH3), γmaxCHCl3 1725 cm-1. The clear solution is refluxed on a steam bath for 2 hr cooled slowly added The white crystalline precipitate is collected washed with ether partitioned between water and ether Sodium bicarbonate is added in portions until the mixture The mixture is extracted with ether the ether solution is washed with saturated sodium chloride solution dried evaporated

反应条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of sodium nitrite (12.4 g.) in water (150 ml.) was dropwise added with stirring at 5° to 7° C. to a solution of ethyl 4-bromoacetoacetate (30 g.) in acetic acid (200 ml.) and the mixture was stirred for 2 hours at 10° C. Water (200 ml.) was added to the reaction mixture and the resultant mixture was extracted with ether (500 ml.). The extract was washed twice with water (200 ml.) and with a sodium chloride aqueous solution (200 ml.) and dried over magnesium sulfate. The solvent was distilled off under reduced pressure to give yellowish brown crystals of ethyl 2-hydroxyimino-4-bromoacetoacetate (a mixture of syn and anti isomers) (32.6 g.). the resultant mixture was extracted with ether (500 ml.) The extract was washed twice with water (200 ml.) and with a sodium chloride aqueous solution (200 ml.) dried over magnesium sulfate The solvent was distilled off under reduced pressure

反应条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of sodium nitrite (12.4 g.) in water (150 ml.) was dropwise added with stirring at 5° to 7° C. to a solution of ethyl 4-bromoacetoacetate (30 g.) in acetic acid (200 ml.) and the mixture was stirred for 2 hours at 10° C. Water (200 ml.) was added to the reaction mixture and the resultant mixture was extracted with ether (500 ml.). The extract was washed twice with water (200 ml.) and with a sodium chloride aqueous solution (200 ml.) and dried over magnesium sulfate. The solvent was distilled off under reduced pressure to give yellowish brown crystals of ethyl 2-hydroxyimino-4-bromoacetoacetate (a mixture of syn and anti isomers) (32.6 g.). the resultant mixture was extracted with ether (500 ml.) The extract was washed twice with water (200 ml.) and with a sodium chloride aqueous solution (200 ml.) dried over magnesium sulfate The solvent was distilled off under reduced pressure

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 10.38 g (0.25 mole) of 57.8% sodium hydride are added to 110 ml of tetrahydrofurane. The mixture is cooled to a temperature between -10° C. and -20° C. whereupon at this temperature 10.08 g (0.125 mole) of ethylene chlorohydrine (III) are added under nitrogen dropwise. The mixture is stirred for 20 minutes, whereupon at the same temperature a solution of 26.18 g (0.125 mole) of ethyl-4-bromoacetoacetate (II) and 35 ml of tetrahydrofurane is added. The reaction mixture is stirred for 20 minutes, allowed to warm to room temperature, kept at this temperature for 6 hours, poured into 270 ml of 1 N hydrochloric acid under cooling and extracted with dichloro methane. The organic layer is dried and evaporated. The residual oil is made free of paraffine by treatment with a 1:1 mixture of acetonitrile and benzene. The product is distilled off in vacuo. Thus 17.47 g of the desired compound are obtained, yield 67%, bp.: 110° C./2 Hgmm. are added under nitrogen dropwise is added kept at this temperature for 6 hours under cooling extracted with dichloro methane The organic layer is dried evaporated The residual oil is made free of paraffine by treatment with a 1:1 mixture of acetonitrile and benzene The product is distilled off in vacuo

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 10.38 g (0.25 mole) of 57.8% sodium hydride are added to 110 ml of tetrahydrofurane. The mixture is cooled to a temperature between -10° C. and -20° C. whereupon at this temperature 10.08 g (0.125 mole) of ethylene chlorohydrine (III) are added under nitrogen dropwise. The mixture is stirred for 20 minutes, whereupon at the same temperature a solution of 26.18 g (0.125 mole) of ethyl-4-bromoacetoacetate (II) and 35 ml of tetrahydrofurane is added. The reaction mixture is stirred for 20 minutes, allowed to warm to room temperature, kept at this temperature for 6 hours, poured into 270 ml of 1 N hydrochloric acid under cooling and extracted with dichloro methane. The organic layer is dried and evaporated. The residual oil is made free of paraffine by treatment with a 1:1 mixture of acetonitrile and benzene. The product is distilled off in vacuo. Thus 17.47 g of the desired compound are obtained, yield 67%, bp.: 110° C./2 Hgmm. are added under nitrogen dropwise is added kept at this temperature for 6 hours under cooling extracted with dichloro methane The organic layer is dried evaporated The residual oil is made free of paraffine by treatment with a 1:1 mixture of acetonitrile and benzene The product is distilled off in vacuo