Methyl chloroformate → tert-Butyl 3-[N-((1R)-1-[(4-chlorophenyl)-methyl]-2-{4-[2-(methoxycarbonylamino)-phenyl]-piperidyl}-2-oxoethyl)carbamoyl](3S)-1,2,3,4-tetrahydroisoquinoline-2-carboxylate

Participants

Reaction Steps

To a 50 mL round-bottomed flask equipped with stirring was added tert-butyl 3-(N-{(1R)-2-[4-(2-aminophenyl)piperidyl]-1-[(4-chlorophenyl)methyl]-2-oxoethyl)carbamoyl)(3S)-1,2,3,4-tetrahydroisoquinoline-2-carboxylate (Example 20) (462 mg, 0.75 mmol) and CH2Cl2 (15 mL) followed by DIEA (0.16 mL, 0.9 mmol). The reaction mixture was stirred for 5 min at RT then treated with methyl chloroformate (Aldrich) (84.6 mg, 0.9 mmol) at 0° C. The reaction mixture was stirred at RT for 12 h then quenched with satd NaHCO3 (15 mL). The organic layer was separated and the aqueous layer was extracted with CH2Cl2 (2×15 mL). The organic fractions were combined, washed with satd NaCl (15 mL), dried over Na2SO4, filtered and concentrated in vacuo. Purification by silica gel chromatography (100% EtOAc) provided the title compound as a white foam (412 mg). MS (ESI, pos. ion) m/z: 675 (M+1); MS (ESI, neg. ion) m/z: 673 (M−1). Calc'd for C11H13ClN4O6: 674.29.

Provenance & Evidence