反应详情

To a solution of 10.9 g of the title compound of Step B in 20 mL of THF was added 23 mL of a commercial 1.0 M solution of n-Bu4NF in THF (containing 5% water) at 15 to 20° C. (water bath cooling) under a nitrogen atmosphere. After 5 minutes, 5.9 g of freshly-ground KOH was added, and then excess Freon® 22 (chlorodifluoromethane) was added through a subsurface tube at a rate sufficient to maintain a slight overpressure. After 20 to 30 minutes, the gas addition was stopped, and the reaction mixture was poured into ice-cold aqueous NH4Cl and extracted with ethyl acetate. The organic phase was washed with water and saturated aqueous NaCl, dried over MgSO4, and concentrated under vacuum. The residue was adsorbed onto silica gel, applied to a column of silica gel and eluted with hexanes/ethyl acetate (4:1 to 3:1 v:v) to obtain an oil. The oil crystallized upon trituration with ether and hexane to produce a white solid that was dried to provide 6.2 g of the title compound of Step C, a compound of this invention, melting at 72-76° C. 1H NMR (CDCl3, 300 MHz) δ 4.3-4.4 (m,1H), 4.8 (m,1H), 5.5 (m,1H), 6.85 (m,1H), 7.0 (m, 2H), 7.4-7.7 (m,9H).

1. temperatureto maintain a slight overpressure
2. waitAfter 20 to 30 minutes
3. additionthe gas addition
4. additionthe reaction mixture was poured into ice-cold aqueous NH4Cl
5. extractionextracted with ethyl acetate
6. washThe organic phase was washed with water and saturated aqueous NaCl
7. dry with materialdried over MgSO4
8. concentrationconcentrated under vacuum
9. washeluted with hexanes/ethyl acetate (4:1 to 3:1 v:v)
10. customto obtain an oil
11. customThe oil crystallized upon trituration with ether and hexane
12. customto produce a white solid
13. customthat was dried