反应详情

To a solution of 4-[(2,2-dimethylpropyl)(2-propen-1-yl)amino]-2-(trifluoromethyl)benzonitrile (1.46 g, 4.95 mmol) in THF/water (20:1, 45 mL) at rt was added a solution of OsO4 (1.02 g of a 2.5 wt % solution in t-BuOH, 0.10 mmol) in THF/water (20:1, 5 mL), followed by NMO (1.22 g, 10.4 mmol) in one portion. The resulting mixture was stirred 22 hours at rt, cooled to 0° C. and sodium bisulfite (0.300 g) was added in one portion. The mixture was stirred 1 h, filtered through a pad of Celite (EtOAc wash) and the filtrate/washings were partitioned between EtOAc/water (required addition of NaCl to separated layers). The aqueous layer was extracted with EtOAc (×1), combined organics were washed with brine and concentrated in vacuo. The residue was dissolved in acetone (50 mL), a solution of NalO4 (2.22 g; 10.4 mmol) in water (20 mL) was added, the mixture was stirred two hours at rt and partially concentrated in vacuo to an aqueous residue. The residue was partitioned between EtOAc/water and the aqueous layer was further extracted with EtOAc (×1). Combined organics were washed (water, brine), dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash chromatography (EtOAc/hexanes), affording 1.20 g of the title compound as a colorless solid: 1H NMR (400 MHz, CDCl3) δ 9.70 (s, 1H), 7.57 (d, J=8.8 Hz, 1H), 6.96 (d, J=2.5 Hz, 1H), 6.74 (dd, J=8.9, 2.7 Hz, 1H), 4.31 (s, 2H), 3.33 (s, 2H), 1.02 (s, 9H).

1. temperaturecooled to 0° C.
2. stirringThe mixture was stirred 1 h
3. filtrationfiltered through a pad of Celite (EtOAc wash)
4. customthe filtrate/washings were partitioned between EtOAc/water (required
5. additionaddition of NaCl
6. customto separated layers)
7. extractionThe aqueous layer was extracted with EtOAc (×1)
8. washcombined organics were washed with brine
9. concentrationconcentrated in vacuo
10. dissolutionThe residue was dissolved in acetone (50 mL)
11. additiona solution of NalO4 (2.22 g; 10.4 mmol) in water (20 mL) was added
12. stirringthe mixture was stirred two hours at rt
13. concentrationpartially concentrated in vacuo to an aqueous residue
14. customThe residue was partitioned between EtOAc/water
15. extractionthe aqueous layer was further extracted with EtOAc (×1)
16. washCombined organics were washed (water, brine)
17. dry with materialdried over Na2SO4
18. filtrationfiltered
19. concentrationconcentrated in vacuo
20. customThe residue was purified by flash chromatography (EtOAc/hexanes)