反应详情

温度

-40 °C

To an ice cold solution of lithium aluminum hydride (0.048 g, 1.33 mmol, 4.0 eq) in tetrahydrofuran (10 mL) to −40° C. is added a solution of 2,2-dichloro-N-((1R,2S)-1-(4-(6-cyanopyridin-3-yl)phenyl)-3-fluoro-1-hydroxypropan-2-yl)acetamide (0.13 g, 0.34 mmol) in tetrahydrofuran (5 mL) at −40° C. Further lithium aluminum hydride is added (0.012 g, 0.33 mmol) three times and reaction mixture is stirred at −40° C. for 4 hours. The reaction mixture is quenched with saturated aqueous sodium sulphate and stirred for 15 minutes followed by filtration. The filtrate is evaporated in vacuo and the crude material purified by column chromatography on silica gel using methanol/CH2Cl2 and ammonia. To the solution of the crude in CH2Cl2 (5 mL) is added trifluoroacetic acid (0.5 mL) and stirred reaction mixture at room temperature for 15 min. Distilled out solvent under vacuum and washed the residue with diethyl ether, and the residue is dissolved in 10% methanol in CH2Cl2 and evaporated to dryness. Washed with n-pentane and dried under vacuum to get the title compound (20 mg): 1HNMR (400 MHz, CDCl3) δ:4.24-4.25 (m, 2H), 4.28-4.32 (m, 0.5H), 4.40-4.44 (m, 0.5H), 4.56-4.60 (m, 0.5H), 4.68-4.72 (m, 0.5H), 4.92 (bs, 1H), 6.02 (bs, 1H), 6.52 (s, 1H), 7.48 (d, J=8.28 Hz, 2H), 7.57 (d, J=10.8 Hz, 1H), 7.73 (d, J=8.04 Hz, 2H), 8.17 (dd, J1=2.28 Hz, J2=8.08 Hz 1H), 8.28 (bs, 2H), 8.65 (d, J=8.84 Hz, 1H), 8.93 (d, 1H, J=2.2 Hz). m/z (CI) 386 [M+H].

1. custom(0.012 g, 0.33 mmol) three times and reaction mixture
2. customThe reaction mixture is quenched with saturated aqueous sodium sulphate
3. stirringstirred for 15 minutes
4. filtrationfollowed by filtration
5. customThe filtrate is evaporated in vacuo
6. customthe crude material purified by column chromatography on silica gel
7. additionTo the solution of the crude in CH2Cl2 (5 mL) is added trifluoroacetic acid (0.5 mL)
8. stirringstirred
9. customreaction mixture at room temperature for 15 min
10. distillationDistilled out solvent under vacuum
11. washwashed the residue with diethyl ether
12. dissolutionthe residue is dissolved in 10% methanol in CH2Cl2
13. customevaporated to dryness
14. washWashed with n-pentane
15. customdried under vacuum