反应详情

Isobutyl chloroformate (0.1 ml) was added dropwise to a tetrahydrofuran solution (2.5 ml) containing N-benzyloxycarbonyl-L-proline (229 mg) and N-methylmorpholine (0.1 ml) at -12° C. to -18° C., and the mixture was stirred at this temperature for nine minutes. An N,N-dimethylformamide solution (1.5 ml) containing 6-methyl-2-(L-valylamino)benzoic acid (142 mg) and N-methylmorpholine (0.075 ml) was added dropwise to the above solution at -15° C., and the resultant solution was stirred at this temperature for 20 minutes and then at room temperature for 45 minutes. Thereafter, 1N hydrochloric acid was added to stop the reaction, and extraction was performed using ethyl acetate. The organic layer was successively washed with 1N hydrochloric acid and brine, dried over sodium sulfate, and concentrated. The residue was purified by flash column chromatography using silica gel to obtain 202 mg of 2-(N-benzyloxycarbonyl-L-prolyl-L-valyl)amino-6-methylbenzoic acid.

1. additionwas added dropwise to the above solution at -15° C.
2. waitat room temperature for 45 minutes
3. customthe reaction, and extraction
4. washThe organic layer was successively washed with 1N hydrochloric acid and brine
5. dry with materialdried over sodium sulfate
6. concentrationconcentrated
7. customThe residue was purified by flash column chromatography