Hydrochloric Acid → 1,3-Thiazol-5-ylmethyl N-((1S,2S,4S)-4-amino-1-benzyl-2-hydroxy-5-phenylpentyl)carbamate

Participants

Reaction Conditions

Reaction Steps

To a 750 gallon glass lined reactor were charged (2S, 3S, 5S)-2-Amino-3-hydroxy-5-(t-butyloxycarbonylamino)-1,6-diphenylhexane--0.5succinic acid salt (75.0 kg, 169 moles), 5-(p-nitrophenyloxycarbonyloxymethyl)thiazole hydrochloride (65.0 kg, 205 moles) and sodium bicarbonate (70.0 kg, 833 moles). Ethyl acetate (826 kg, 918 L) was added and the agitator was started. Tap water (788 kg) was added and the mixture was warmed to 30° C. and stirred for 2.5 hours until all of the solids were dissolved. After settling for 30 minutes, the aqueous layer was separated and discarded. The organic layer was warmed to 60° C. and stirred for 12 hours. The solution was then cooled to 30° C. and 28% ammonia water (9.0 kg, 148 moles) was added. The mixture was stirred for 3 hours at 25°-30° C. The mixture was washed three times with aqueous 10% potassium carbonate solution (903 kg each time). The aqueous layers were drained and discarded after each wash. Concentrated hydrochloric acid (59.0 kg, 600 moles) was added to the ethyl acetate solution and warmed to 50° C. with stirring for 3 hours.

Provenance & Evidence