Triethylamine → 4-[[(4-cyano-4-phenyl-1-piperidinyl)carbonyl]amino]-L-phenylalanine

Participants

Reaction Steps

4-Amino-N-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-phenylalanine on Wang resin (300 mg, 0.228 mmol) obtained from Example 62 was placed in a vessel fitted with a glass frit and was washed with dichloromethane (2×10 mL), methanol (2×10 mL) and dichloromethane (2×10 mL). To the resin was added carbonyl diimidazole (0.22 g, 1.4 mmol) and triethylamine (0.38 mL, 2.7 mmol) in 3 mL of dichloromethane. The mixture was agitated over night. The mixture was then filtered and washed with dichloromethane (3×5 mL). To the resin was added 4-cyano-4-phenylpiperidine hydrochloride (0.25 g, 1.14 mmol) and DMAP (0.14 g, 1.14 mmol) in 3 mL of N-methylpyrrolidinone. The resulting mixture was agitated for 3 hours. The reaction mixture was then filtered and washed with dichloromethane (2×10 mL), methanol (2×10 mL), dimethylformamide (2×10 mL) and methanol (2×10 mL). Cleavage of the Fmoc group was effected with 25% piperidine in N-methylpyrrolidinone (2×15 min to give 4-[[(4-cyano-4-phenyl-1-piperidinyl)carbonyl]amino]-L-phenylalanine on Wang resin.

Provenance & Evidence