反应详情

温度

-78 °C

(3S,5R)-1-[4-(4-chlorophenoxy)phenyl]-3-allyl-5-[3-(trifluoromethyl)phenyl]pyrrolidin-2-one (56 mg, 0.119 mmol) is dissolved in 3 mL of a 2:1 mixture of CH2Cl2-MeOH and is cooled to −78° C. Ozone is bubbled through the solution until a blue color persisted and then nitrogen is bubbled through until it is clear. NaBH4 (2.5 eq) is added and the reaction mixture is allowed to warm to room temperature. The mixture is stirred for 2 h, and then most of the solvent is removed by evaporation in vacuo. Water is added (10 mL) and the aqueous layer is extracted with ethyl acetate (5×10 mL). The combined extracts are washed with brine (10 mL), dried over Na2SO4, filtered and evaporated. The residue is purified on silica gel (0-55% ethyl acetate in hexane) to give (3R,5R)-1-[4-(4-chlorophenoxy)phenyl]-5-[3-(trifluoromethyl)phenyl]-3-(2-hydroxyethyl)pyrrolidin-2-one (51 mg, 89%) as a colorless oil. 1H NMR (CDCl3, 400 MHz) δ 7.51-7.46 (m, 1H), 7.44-7.37 (m, 2H), 7.36-7.30 (m, 3H), 7.21-7.16 (m, 2H), 6.87-6.78 (m, 4H), 5.21 (dd, J=10.5, 2.0 Hz, 1H), 3.85-3.68 (m, 2H), 2.97-2.85 (m, 1H), 2.45-2.32 (m, 1H), 2.26-2.15 (m, 2H), 2.10-1.98 (m, 1H), 1.80-1.69 (m, 1H). HPLC-MS calculated for C25H21ClF3NO3 (M+H+) 476.12, found 476.10.

1. customOzone is bubbled through the solution until a blue color
2. customnitrogen is bubbled through until it
3. temperatureto warm to room temperature
4. custommost of the solvent is removed by evaporation in vacuo
5. additionWater is added (10 mL)
6. extractionthe aqueous layer is extracted with ethyl acetate (5×10 mL)
7. washThe combined extracts are washed with brine (10 mL)
8. dry with materialdried over Na2SO4
9. filtrationfiltered
10. customevaporated
11. customThe residue is purified on silica gel (0-55% ethyl acetate in hexane)