Water → HCID 58058025, compound

Participants

Reaction Steps

39.5 kg of (R)-methyl 2-(2-(benzyloxycarbonylamino)ethylamino)-3-t-butoxypropanoate was dissolved in 276 L of methanol in a reactor; purged with nitrogen; 5.9 kg of palladium/carbon (10% water mixture) was added and stirred for 3 hours while the hydrogen pressure was maintained at 10 bar. The reaction solution was filtered, concentrated under reduced pressure, and then again azeotroped by adding 30 L of isopropylether. 158 L (115 kg) of isopropylether, 39 L (35 kg) of ethyl acetate, and 36.4 kg of silica gel were added to a concentrated solution, stirred for 1 hour, decompression-filtered, and then concentrated under reduced pressure. A concentrated residue was azeotroped by adding 30 L of methanol, and then a concentrated solution and 221 L of methanol were added to a reactor. After purging with nitrogen, 11.85 kg of palladium/carbon (10% water mixture) was added, and then stirred for 6 hours while hydrogen pressure was maintained at 15 bar. The reaction solution was filtered, and then concentrated under reduced pressure. An aqueous layer was isolated in twice by adding 80 L of isopropylether and 80 L of purified water to the concentrated solution. An organic layer was isolated after adding methylene chloride/isopropanol=5:1 (126 L) to the aqueous layer and then stirring in 5 times. The organic layer was dehydration-filtered with 50 kg of sodium sulfate to obtain 9.7 kg of a title compound.

Provenance & Evidence