乙基 2-溴-4-苯基丁酸乙酯

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

实验步骤: Following the procedure described in Example 42(h), 0.40 g of t-butyl α-[6-amino-2-(2-furyl)-5-oxoperhydro-1,4-thiazepin-4-yl]acetate [prepared as described in step (f) above] was N-alkylated using 0.68 g of ethyl 2-bromo-4-phenylbutyrate. The resulting product was subjected to silica gel column chromatography eluted with a 1:20 by volume mixture of ethyl acetate and methylene chloride, to separate it into two isomers, A and B, (ascribed to the asymmetric carbon atom to which the phenethyl group is attached). eluted with a 1:20 by volume mixture of ethyl acetate and methylene chloride to separate it into two isomers

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

实验步骤: Following the procedure described in Example 42(h), 0.40 g of t-butyl α-[6-amino-2-(2-furyl)-5-oxoperhydro-1,4-thiazepin-4-yl]acetate [prepared as described in step (f) above] was N-alkylated using 0.68 g of ethyl 2-bromo-4-phenylbutyrate. The resulting product was subjected to silica gel column chromatography eluted with a 1:20 by volume mixture of ethyl acetate and methylene chloride, to separate it into two isomers, A and B, (ascribed to the asymmetric carbon atom to which the phenethyl group is attached). eluted with a 1:20 by volume mixture of ethyl acetate and methylene chloride to separate it into two isomers

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

实验步骤: Following the procedure described in Example 42(h), 0.40 g of t-butyl α-[6-amino-5-oxo-2-(2-thienyl)perhydro-1,4-thiazepin-4-yl]acetate [prepared as described in step (g) above] was N-alkylated using 0.64 g of ethyl 2-bromo-4-phenylbutyrate. The resulting product was subjected to silica gel column chromatography eluted with a 1:20 by volume mixture of ethyl acetate and methylene chloride, to separate it into two isomers, A and B, (ascribed to the asymmetric carbon atom to which the phenethyl group is attached). eluted with a 1:20 by volume mixture of ethyl acetate and methylene chloride to separate it into two isomers

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

实验步骤: Following the procedure described in Example 42(h), 0.40 g of t-butyl α-[6-amino-5-oxo-2-(2-thienyl)perhydro-1,4-thiazepin-4-yl]acetate [prepared as described in step (g) above] was N-alkylated using 0.64 g of ethyl 2-bromo-4-phenylbutyrate. The resulting product was subjected to silica gel column chromatography eluted with a 1:20 by volume mixture of ethyl acetate and methylene chloride, to separate it into two isomers, A and B, (ascribed to the asymmetric carbon atom to which the phenethyl group is attached). eluted with a 1:20 by volume mixture of ethyl acetate and methylene chloride to separate it into two isomers

反应条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 0.47 g of t-butyl α-[6-amino-5-oxo-2-(3-thienyl)perhydro-1,4-thiazepin-4-yl]acetate [prepared as described in step (d) above] and 0.8 g of ethyl 2-bromo-4-phenylbutyrate in 7 ml of dimethylformamide was added 1.0 g of sodium carbonate. The reaction mixture was stirred at 70° C. for 18 hours and then dissolved in ethyl acetate and an aqueous solution of sodium chloride. The ethyl acetate layer was separated, washed with water and dried over anhydrous magnesium sulfate, and the solvent was evaporated off. The residue was subjected to silica gel column chromatography using a 1:20 by volume mixture of ethyl acetate and methylene chloride to give two isomers, A and B (ascribed to the asymmetric carbon atom to which the phenethyl group is attached). The first eluted isomer A was an oily compound in a yield of 0.27 g. The ethyl acetate layer was separated washed with water dried over anhydrous magnesium sulfate the solvent was evaporated off by volume mixture of ethyl acetate and methylene chloride to give two isomers

反应条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 0.47 g of t-butyl α-[6-amino-5-oxo-2-(3-thienyl)perhydro-1,4-thiazepin-4-yl]acetate [prepared as described in step (d) above] and 0.8 g of ethyl 2-bromo-4-phenylbutyrate in 7 ml of dimethylformamide was added 1.0 g of sodium carbonate. The reaction mixture was stirred at 70° C. for 18 hours and then dissolved in ethyl acetate and an aqueous solution of sodium chloride. The ethyl acetate layer was separated, washed with water and dried over anhydrous magnesium sulfate, and the solvent was evaporated off. The residue was subjected to silica gel column chromatography using a 1:20 by volume mixture of ethyl acetate and methylene chloride to give two isomers, A and B (ascribed to the asymmetric carbon atom to which the phenethyl group is attached). The first eluted isomer A was an oily compound in a yield of 0.27 g. The ethyl acetate layer was separated washed with water dried over anhydrous magnesium sulfate the solvent was evaporated off by volume mixture of ethyl acetate and methylene chloride to give two isomers

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

实验步骤: 0.85 g of t-butyl α-[6-amino-2-(2-naphthyl)-5-oxoperhydro-1,4-thiazepin-4-yl]acetate [prepared as described in step (g) above] was subjected to N-alkylation with 1.08 g of ethyl 2-bromo-4-phenylbutyrate in the same manner as described in Example 36(h). The reaction product was subjected to silica gel column chromatography, using a 1:30 by volume mixture of ethyl acetate and methylene chloride, to separate it into two isomers, A and B (ascribed to the asymmetric carbon atom to which the phenethyl group is attached). to separate it into two isomers

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

实验步骤: 0.85 g of t-butyl α-[6-amino-2-(2-naphthyl)-5-oxoperhydro-1,4-thiazepin-4-yl]acetate [prepared as described in step (g) above] was subjected to N-alkylation with 1.08 g of ethyl 2-bromo-4-phenylbutyrate in the same manner as described in Example 36(h). The reaction product was subjected to silica gel column chromatography, using a 1:30 by volume mixture of ethyl acetate and methylene chloride, to separate it into two isomers, A and B (ascribed to the asymmetric carbon atom to which the phenethyl group is attached). to separate it into two isomers

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

实验步骤: 344 mg of t-butyl α-[6(R)-amino-5-oxo-3(S)-(2-thienyl)perhydro-1,4-thiazepin-4-yl]acetate [prepared as described in step (g) above] were subjected to N-alkylation with 406 mg of ethyl 2-bromo-4-phenylbutyrate in the manner described in Example 1(h). The reaction product was subjected to silica gel column chromatography using a 1:20 by volume mixture of ethyl acetate and methylene chloride as eluent, which separated the compound into two isomers, A and B, (ascribed to the asymmetric carbon atom to which the phenethyl group is attached). Isomer A (in which the carbon attached to the phenethyl group had the R-configuration) was eluted first as an oily compound in a yield of 0.17 g. which separated the compound into two isomers was eluted first as an oily compound in a yield of 0.17 g

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

实验步骤: 344 mg of t-butyl α-[6(R)-amino-5-oxo-3(S)-(2-thienyl)perhydro-1,4-thiazepin-4-yl]acetate [prepared as described in step (g) above] were subjected to N-alkylation with 406 mg of ethyl 2-bromo-4-phenylbutyrate in the manner described in Example 1(h). The reaction product was subjected to silica gel column chromatography using a 1:20 by volume mixture of ethyl acetate and methylene chloride as eluent, which separated the compound into two isomers, A and B, (ascribed to the asymmetric carbon atom to which the phenethyl group is attached). Isomer A (in which the carbon attached to the phenethyl group had the R-configuration) was eluted first as an oily compound in a yield of 0.17 g. which separated the compound into two isomers was eluted first as an oily compound in a yield of 0.17 g

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

实验步骤: 0.22 g of the isomer of t-butyl α-[6-amino-5-oxo-2-phenylperhydro-1,4-thiazepin-4-yl]acetate [prepared as described in step (h) above] was subjected to N-alkylation with 0.28 g of ethyl 2-bromo-4-phenylbutyrate in the same manner as described in Example 1(h). The resulting product was subjected to silica gel column chromatography, using a 1:20 by volume mixture of ethyl acetate and methylene chloride as the eluent. From the fraction first eluted was obtained 0.14 g of t-butyl α-{6-[1-ethoxycarbonyl-3-phenylpropylamino]-5-oxo-2-phenylperhydro-1,4-thiazepin-4-yl}acetate as an oil. From the fraction first eluted

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

实验步骤: 0.22 g of the isomer of t-butyl α-[6-amino-5-oxo-2-phenylperhydro-1,4-thiazepin-4-yl]acetate [prepared as described in step (h) above] was subjected to N-alkylation with 0.28 g of ethyl 2-bromo-4-phenylbutyrate in the same manner as described in Example 1(h). The resulting product was subjected to silica gel column chromatography, using a 1:20 by volume mixture of ethyl acetate and methylene chloride as the eluent. From the fraction first eluted was obtained 0.14 g of t-butyl α-{6-[1-ethoxycarbonyl-3-phenylpropylamino]-5-oxo-2-phenylperhydro-1,4-thiazepin-4-yl}acetate as an oil. From the fraction first eluted