Triethylamine hydrochloride → HCID 86607893, compound

Participants

Reaction Steps

A mixture of 1-tert-butyl 3-methyl (3R,4R)-3-hydroxy-4-[({4-[(2-methylquinolin-4-yl)methoxy]phenyl}sulfonyl)amino]piperidine-1,3-dicarboxylate (1.59 g, 2.72 mmol), methanol (10 mL), THF (10 mL) and 1N sodium hydroxide (10.9 mL, 4 eq) was stirred overnight. Triethylamine hydrochloride (2.25 g, 16.32 mmol, 6 eq) was added and the resulting mixture was stirred for awhile and then concentrated in vacuo. The residue was dried by azeotropic evaporation with toluene and then dried under high vacuum for 5 h. This crude carboxylic acid was dissolved in DMF (30 mL) and diisopropylethylamine (1.9 mL, 10.88 mmol, 4.0 eq), BOP reagent (1.56 g, 3.54 mmol, 1.3 eq) and O-tert-butylhydroxylamine hydrochloride (512 mg, 4.08 mmol, 1.5 eq) were added. The reaction was stirred overnight, and then diluted with ethyl acetate and water. The organic phase was washed with water three times. The aqueous layer was re-extracted with ethyl acetate. The combined organic layers were washed with brine, dried over MgSO4, and concentrated. The residue was purified by chromatography with 65-70% ethyl acetate/hexane to yield 740 mg (42% in two steps) of tert-butyl (3R,4R)-3-[(tert-butoxyamino)carbonyl]-3-hydroxy-4-[({4-[(2-methylquinolin-4-yl)methoxy]phenyl}sulfonyl)amino]piperidine-1-carboxylate as white solid. MS: (M+H)+=643.1.

Provenance & Evidence