N-Boc-L-cysteine ethyl ester

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 14.7 g (59 mmol) of N-Boc-L-cysteine ethyl ester dissolved in 300 ml of dimethylformamide are added dropwise at 0° to a suspension of 2.49 g (64.8 mmol) of sodium hydride (60% in oil) in 200 ml of dimethylformamide and the mixture is stirred at 0° for 30 minutes. Subsequently, 8.37 g (62 mmol) of bromomethylcyclopropane in 30 ml of dimethylformamide are added dropwise thereto. The solution is stirred at room temperature overnight. The dimethylformamide is evaporated under reduced pressure, the residue is partitioned between ether and water and the aqueous phase is extracted 4 times with ether. The combined organic phases are washed twice with water and twice with saturated sodium chloride solution, dried over sodium sulphate and evaporated under reduced pressure. For purification, the residue is chromatographed on silica gel using a 1:19 mixture of ethyl acetate and hexane as the eluent. There are obtained 8.4 g of tert-butyl rac-[2-[(cyclopropylmethyl)thio]-1-(ethoxycarbonyl)ethyl]carbamate as a colourless oil, MS: 304 (M+H)+. The solution is stirred at room temperature overnight The dimethylformamide is evaporated under reduced pressure the residue is partitioned between ether and water the aqueous phase is extracted 4 times with ether The combined organic phases are washed twice with water and twice with saturated sodium chloride solution dried over sodium sulphate evaporated under reduced pressure For purification the residue is chromatographed on silica gel using a 1:19 mixture of ethyl acetate and hexane as the eluent

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 14.7 g (59 mmol) of N-Boc-L-cysteine ethyl ester dissolved in 300 ml of dimethylformamide are added dropwise at 0° to a suspension of 2.49 g (64.8 mmol) of sodium hydride (60% in oil) in 200 ml of dimethylformamide and the mixture is stirred at 0° for 30 minutes. Subsequently, 8.37 g (62 mmol) of bromomethylcyclopropane in 30 ml of dimethylformamide are added dropwise thereto. The solution is stirred at room temperature overnight. The dimethylformamide is evaporated under reduced pressure, the residue is partitioned between ether and water and the aqueous phase is extracted 4 times with ether. The combined organic phases are washed twice with water and twice with saturated sodium chloride solution, dried over sodium sulphate and evaporated under reduced pressure. For purification, the residue is chromatographed on silica gel using a 1:19 mixture of ethyl acetate and hexane as the eluent. There are obtained 8.4 g of tert-butyl rac-[2-[(cyclopropylmethyl)thio]-1-(ethoxycarbonyl)ethyl]carbamate as a colourless oil, MS: 304 (M+H)+. The solution is stirred at room temperature overnight The dimethylformamide is evaporated under reduced pressure the residue is partitioned between ether and water the aqueous phase is extracted 4 times with ether The combined organic phases are washed twice with water and twice with saturated sodium chloride solution dried over sodium sulphate evaporated under reduced pressure For purification the residue is chromatographed on silica gel using a 1:19 mixture of ethyl acetate and hexane as the eluent

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: An oven-dried 25 mL one-necked round-bottomed flask equipped with a septum and a stir bar was charged with compound 17 (0.006 g, 0.015 mmol) in CH2Cl2/MeOH 1:1 (5 mL). N-Boc-L-cysteine ethyl ester (0.0036 g, 0.015 mmol) was added in one portion and the mixture mas stirred at rt for 10 min. The consumption of the starting material was monitored by TLC (AcOEt/n-hexane 1:1). The solution was then concentrated under reduced pressure and the reaction residue was purified by silica gel flash column chromatography, eluting with AcOEt/n-hexane 1:1, to provide 0.006 g of the title compound as a 1:1 mixture of two inseparable diastereomers (d1 and d2) in a 60% yield. An oven-dried 25 mL one-necked round-bottomed flask equipped with a septum and a stir bar The consumption of the starting material The solution was then concentrated under reduced pressure the reaction residue was purified by silica gel flash column chromatography eluting with AcOEt/n-hexane 1:1