反应详情

温度

60 °C

1 M Aqueous sodium hydroxide solution (1.6 mL, 1.6 mmol) was added to a solution of (S)-methyl 2-(tert-butoxy)-2-(2-methyl-4-(4-(trifluoromethyl)phenyl)-5,6,7,8-tetrahydro benzo[4,5]thieno[2,3-b]pyridin-3-yl)acetate (75 mg, 0.15 mmol) in 1:1 tetrahydrofuran/industrial methylated spirit (4 mL) at room temperature. The resulting mixture was heated at 60° C. 1.5 h. The resulting solution was concentrated in vacuo and the residue was dissolved in water (10 mL). The aqueous solution was adjusted to pH 4 by the addition of 2 M aqueous hydrochloric acid solution and the resulting suspension was extracted with dichloromethane (20 mL). The organic layer was washed with brine, dried (MgSO4) and concentrated in vacuo to give the crude product as a pale yellow solid. This was purified by flash column chromatography on silica eluting with methanol in dichloromethane (5%) to give the title compound (40.3 mg, 56%) as a pale yellow solid. 1H NMR (400 MHz, CDCl3) δ=1.01 (s, 9H), 1.89-1.30 (m, 6H), 2.71 (s, 3H), 2.90-2.75 (m, 2H), 5.02 (s, 1H), 7.48-7.34 (m, 1H), 7.90-7.64 (m, 3H). LCMS (run time=5 minutes, basic): Rt=3.30 minutes; m/z 478.01 [M+H+].

1. custom1.5 h
2. concentrationThe resulting solution was concentrated in vacuo
3. dissolutionthe residue was dissolved in water (10 mL)
4. additionThe aqueous solution was adjusted to pH 4 by the addition of 2 M aqueous hydrochloric acid solution
5. extractionthe resulting suspension was extracted with dichloromethane (20 mL)
6. washThe organic layer was washed with brine
7. dry with materialdried (MgSO4)
8. concentrationconcentrated in vacuo
9. customto give the crude product as a pale yellow solid
10. customThis was purified by flash column chromatography on silica eluting with methanol in dichloromethane (5%)