Cis-4-Phenylthio-L-proline

Sodium bicarbonate cis-4-Phenylthio-L-proline Hydrogen chloride Dicyclohexylamine Potassium bisulfate... 

This N-carbobenzyloxy-cis-4-phenylthio-L-proline cyclohexylamine salt is suspended in 25 ml of ethyl acetate, stirred, and treated with 25 ml of 1 N hydrochloric acid. When two clear layers are obtained, they are separated and the aqueous phase is extracted with additional ethyl acetate (3x25 ml). The combined organic layers are dried (MgS04) and the solvent evaporated to give... 

A solution of 3.0 g (0.0094 mole) of (cis)-4-phenylthio-L-proline hydrobromide in 25 ml of water is stirred, cooled to 5°C and 15 ml of 20% sodium carbonate are added. This mixture is treated with 2.0 g (0.011 mole) of D-3-acetylthio-2-methylpropionyl chloride in 5 ml of ether during the course of 10 min with the intermittent addition of 3.0 g of sodium carbonate to maintain the pH at 8.0 to 8.4). The mixture is stirred in the ice-bath for an additional hour, 25 ml of water are added and then a solution of 5 ml of concentrated hydrochloric acid in 25 ml of water. The strongly acid solution is saturated with sodium chloride and extracted with 50 ml of ethyl acetate (four times). The organic phases are combined, dried, filtered and solvent evaporated to give 3.8 g of a pale yellow viscous oil. The dicyclohexylamine salt following trituration with 15 ml of acetonitrile one obtains 2.4 g of colorless solid 1-[D-... 

This l-[D-3-(acetylthio)-2-methyl-l-oxopropyl]-cis-4-phenylthio-L-proline dicyclohexylamine salt is treated with 30 ml of 10% potassium bisulfate and extracted into ethyl acetate, cooled in an ice bath and treating portionwise with 60 ml of 10% potassium bisulfate. The clear layers are separated and the aqueous portion extracted with 60 ml of ethyl acetate (2 times). The organic phases are combined, dried (MgS04), filtered and the solvent is evaporated to give 2.0 g (59%) of glass-like l-[D-3-(acetylthio)-2-methyl-l-oxopropyl]-cis-... 

To a solution of this cis-l-[D-3-(benzoylthyo)-2-methyl-l-oxopropyl]-4-(phenylthio)-L-proline hydrochloride 11.8 g (0.027 mole) in 70 ml of acetonitrile there is added about 6.0 g of dicyclohexylamine in 25 ml of ether. A white crystalline precipitate forms immediately. After standing overnight in the cold room, the solid is filtered and washed with ether to yield (cis)-l-[D-3-(benzoylthio)-2-methyl-l-oxopropyl]-4-(phenylthio)-L-proline, dicyclohexylamine salt (1 1). 

The slightly moist (cis)-l-[D-3-(benzoylthio)-2-methyl-l-oxopropyl]-4-(phenylthio)-L-proline dicyclohexylamine salt is stirred for 2.5 h in a mixture of 300 ml of ethyl acetate and 200 ml of 10% potassium bisulfate. Two clear layers form. The aqueous layer is extracted with two 200 ml portions of ethyl acetate and the combined organic layers are dried (MgS04). The solvent is removed to yield 10.1 g of foamy solid (cis)-l-[D-3-(benzoylthio)-2-methyl-l-oxopropyl]-4-(phenylthio)-L-proline melting point 42-44°C. 

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