Trifluoroacetic acid → Benzyl (S)-1-((1S,2R,4R)-2-acetamido-4-aminocyclohexyl)-2-oxopyrrolidin-3-ylcarbamate

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Reaction Steps

A sample of tert-butyl (1R,3R,4S)-3-acetamido-4-((S)-3-(benzyloxycarbonylamino)-2-oxopyrrolidin-1-yl)cyclohexylcarbamate (43.2 g, 88 mmol; see Example 1, Step 6) was dissolved in dichloromethane (200 mL). The solution was charged with TFA (100 mL), stirred for 2.5 h, and concentrated in vacuo. The residue was re-dissolved in dichloromethane (200 mL) and the resultant solution was added dropwise to a stirring solution of pure diethyl ether (2.0 L). The white solid was collected with ether washes and then dissolved in a basic saline solution (2.0 M in NaCl and 1.0 M in K2CO3, 350 mL total). Dichloromethane (1.2 L) was added, and the two phases were mixed vigorously before being separated. The aqueous phase was extracted with dichloromethane (3×450 mL). The organic extracts were combined, dried (MgSO4), filtered, and concentrated in vacuo to afford benzyl (S)-1-((1S,2R,4R)-2-acetamido-4-aminocyclohexyl)-2-oxopyrrolidin-3-ylcarbamate (34.8 g, quantitative) as a microcrystalline solid after pumping on high vacuum. LC/MS found [M+H]+=389.5.

Provenance & Evidence