反应详情

A solution of 500 mg (1.46 mmol) of 5-(4-fluorophenyl)-6-[4-(methylsulfonyl)phenyl]spiro[2.4]hept-5-ene (from Step 11) in 7 mL of dichloromethane was treated with 480 mg (55% peroxyacid, 1.53 mmol) of m-chloroperoxybenzoic acid (MCPBA). The reaction was stirred at ambient temperature for 2.5 hours, washed with aqueous saturated sodium bisulfite, dried (MgSO4), and concentrated in vacuo to give a mixture of desired expoxide intermediate and m-chlorobenzoic acid; this crude mixture in 10 mL of acetic acid and 1 mL of water was subsequently treated with 500 mg (6.1 mmol) of sodium acetate and stirred at 80° C. for 10 hours. The reaction mixture was cooled to ambient temperature and concentrated in .vacuo. The residue was partitioned between water and ethyl acetate; the organic phase was washed with aqueous saturated sodium bicarbonate, water, brine, dried (MgSO4), and reconcentrated in vacuo. Purification by silica gel chromatography gave 317 mg (64%) of 5-(4-fluorophenyl)-6-[4-(methylsulfonyl)phenyl]spiro[2.4]hepta-4,6-diene as a colorless solid: mp 119°-128° C. (dec); NMR (CDCl3) δ 1.81 (s, 4H), 3.06 (s, 3H), 6.22 (d, J=2 Hz, 1H), 6.36 d, J=2 Hz, 1H), 6.95 (t, J=8 Hz, 2H), 7.02-7.18 (m, 2H), 7.33 (d, J=8 Hz, 2H), 7.80 (d, J=8 Hz, 2H). MS (FAB) m/e (rel intensity) 347 (100) (M+Li). HRMS. Calc'd for C20H17FO2S: 340.0933. Found: 340.0952. Anal. Calc'd for C20H17FO2S: C, 69.29; H, 4.97; F, 5.45. Found: C, 69.21; H, 5.23; F, 5.81.

1. washwashed with aqueous saturated sodium bisulfite
2. dry with materialdried (MgSO4)
3. concentrationconcentrated in vacuo
4. customto give
5. stirringstirred at 80° C. for 10 hours
6. temperatureThe reaction mixture was cooled to ambient temperature
7. concentrationconcentrated in .vacuo
8. customThe residue was partitioned between water and ethyl acetate
9. washthe organic phase was washed with aqueous saturated sodium bicarbonate, water, brine
10. dry with materialdried (MgSO4)
11. customPurification by silica gel chromatography