反应详情

To a solution of Part A compound (0.418 g, 1.29 mmol, 1.00 eq.) in dichloromethane (2.2 mL) under argon at 0° C. was added trifluoroacetic acid (1.5 mL, 19.5 mmol, 15.1 eq.). After 4.0 hr, trifluoroacetic acid (5 mL, 64.8 mmol, 5.44 eq.) was added. After 5 hr, the reaction mixture was concentrated in vacuo to give the crude TFA salt of Part A compound. To a solution of Boc-4-nitro-L-phenylalanine (0.441 g, 1.42 mmol, 1.10 eq.) and 1-hydroxybenzo-triazole hydrate (0.193 g, 1.43 mmol, 1.10 eq.) in dimethylformamide (5.0 mL) at 0° C. was added 1-(3-dimethylaminopropyl)-2-ethylcarbodiimide hydrochloride (0.273 g, 1.43 mmol, 1.10 eq.). After 0.5 hr, a solution of crude TFA salt of Part A compound (1.29 mmol, 1.00 eq.) in dimethylformamide (3.0 mL) was added, which was then followed by 4-methylmorpholine (0.5 mL, 4.55 mmol, 3.52 eq.). After 21 hr, the reaction mixture was poured into a brine/water solution (1:1) and extracted with ethyl acetate twice. The organic layers were combined and washed with aqueous 0.25M potassium hydrogen sulfate, water, aqueous saturated sodium bicarbonate and water, successively. The organic layer was concentrated in vacuo to give title compound (0.651 g, 98.0%):

1. waitAfter 21 hr
2. extractionextracted with ethyl acetate twice
3. washwashed with aqueous 0.25M potassium hydrogen sulfate, water, aqueous saturated sodium bicarbonate and water
4. concentrationThe organic layer was concentrated in vacuo