反应详情

温度

140 °C

1,1-Dimethylethyl (2S)-4-{[4-(acetylamino)-2-methylphenyl]methyl}-2-methyl-1-piperazinecarboxylate (D53) (497 mg, 1.4 mmol) and KOH (1M aq. soln., 5 ml) were combined in MeOH (5 ml) and heated to 140° C. for 1 h in a microwave reactor. The reaction mixture was diluted with MeOH (5 ml) and heated for a total of 4 h 55 minutes at 130° C. in the microwave. The reaction mixture was concentrated to remove the MeOH and partitioned between DCM and water. The organic layer was dried and concentrated to give the crude product which was purified by column chromatography. Elution with 0-100% diethyl ether/petroleum ether followed by a column flush with 10% (2M NH3 in MeOH) in DCM yielded the title compound as a yellow oil (233 mg). δH (CDCl3, 400 MHz) 6.97 (1H, d), 6.52 (1H, d), 6.46 (1H, dd), 4.17 (1H, br.s), 3.76 (1H, d), 3.57 (2H, br.s), 3.29 (2H, m), 3.01 (1H, td), 2.70 (1H, d), 2.56 (1H, d), 2.30 (3H, s), 2.10 (1H, dd), 1.90 (1H, m), 1.45 (9H, s), 1.18 (3H, d). MS (AP+): 342.3 (MNa+), no molecular (MH+) ion observed.

1. temperatureheated for a total of 4 h 55 minutes at 130° C. in the microwave
2. concentrationThe reaction mixture was concentrated
3. customto remove the MeOH
4. custompartitioned between DCM and water
5. customThe organic layer was dried
6. concentrationconcentrated
7. customto give the crude product which
8. customwas purified by column chromatography
9. washElution with 0-100% diethyl ether/petroleum ether
10. customflush with 10% (2M NH3 in MeOH) in DCM