Acetylcysteamine → [2-(Acetylamino)ethyl]-6-ethyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid, (4-nitrophenyl)methyl ester

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Reaction Steps

Preparation of trans (±)-3-[[2-(acetylamino)ethyl)thio]-6-ethyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid, (4-nitrophenyl)methyl ester (XVII, R=CH3CH2 --, R'"=CH3CONH--CH2 --CH2 --, R4 = ##STR19## A solution of the bicyclic keto ester obtained in step (c) above (XV R=CH3CH2 --) (2.49 g) in acetonitrile (15 ml) is cooled to 0° C. and diisopropylethylamine (1.42 ml) is added. Then chlorodiphenylphosphate (1.72 ml) is added drop by drop keeping the temperature at 0°/-2° C. Stirring is continued for 15 minutes at 0° C., after which thin layer chromatography confirms the complete transformation of the bicyclic keto ester XV into the enol phosphate derivative XVI (R=CH3CH2 --). An additional portion of diisopropylethylamine (1.55 ml) is added followed by the slow addition of N-acetylcysteamine (1.07 g) dissolved in acetonitrile (5 ml). The reaction mixture is then stirred at 0° C. for 30 minutes and the solid which precipitates is filtered, washed with cold acetonitrile (10 ml) and diethyl ether (20 ml), and dried in vacuo at room temperature yielding 2.03 g of trans (±)-3-[[2 -(acetylamino)ethyl]-6-ethyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid, (4-nitrophenyl)methyl ester which melts at 174°-76° C. Additional 0.46 g of equally pure product is obtained on cooling the filtrate to -20° C. for 2 hours.

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