Hydrochloric Acid → HCID 67004551, compound

Participants

Reaction Conditions

Reaction Steps

Water (3 ml) is added to the stirred reaction mixture containing (3R,4R)-4-(tert-butoxy-carbonyl-methyl-amino)-5-(3,4-dichloro-phenyl)-3-hydroxy-pentanoic acid methyl ester (5) at 18-22° C., then lithium hydroxide monohydrate (0.755 g, 18 mmol) is added. Stirring at 18-22° C. is continued for approx. 2 hours. Hydrochloric acid (approx. 12.6 ml of 2N, 25.2 mmol)) is added over a period of approx. 30 minutes, until pH 1.7-2.2 is obtained. Toluene (12 ml) is added to the stirred mixture and stirring at 18-22° C. is continued for approx. 10 minutes. Stirring is stopped and the layers are allowed to separate. The lower, aqueous layer is separated and the upper, organic layer is extracted with water (12 ml). Stirring is stopped and the lower, aqueous layer is separated. The organic layer is filtrated over a filter charged with anhydrous sodium sulfate (3 g) in order to remove remains of water and 1,3-dicyclohexyl urea, the latter originating from step 1. The filter cake is rinsed with toluene (2 ml), then N,N-dimethylformamide (12 ml) is added to the filtrate. The resulting solution is concentrated by distilling toluene at a mantle temperature of approx. 50° C. under reduced pressure, until the volume of the residue is approx. 14 ml. This resulting solution, containing (3R,4R)-4-(tert-butoxycarbonyl-methyl-amino)-5-(3,4-dichloro-phenyl)-3-hydroxy-pentanoic acid (6) is used as such in the following step.

Provenance & Evidence