反应详情

A soltuion of 3 g(19.4 mmol) of 5-chlorovaleryl chloride in 15 ml of anhydrous THF was added dropwise with vigorous stirring over 15 min. under nitrogen, to a solution of ethylmagnesium bromide (15 mL of 3M in ether) in 15 mL of anhydrous THF at -5° C. The reaction was allowed to warm up to room temperature and stirred for 2 hours. After cooling the mixture to 0° C. it was quenched with diluted hydrochloric acid. The mixture was extracted with ether, washed with water, dried over anh. MgSO4, filtered and evaporated. The residue was flash chromatographed through silicagel in CH2Cl2 to give 2.7 g (84%) of the chloroalcohol as a colorless liquid (5-hydroxy-5-ethyl-heptyl chloride). To a stirred solution of 1.32 g (10 mmol) of thiophenol and 1.32 g (11.3 mmol) of potassium tret.-butoxide was added 1.5 g (10 mmol) of the heptyl chloride as prepared above in 5 ml of anhydrous dimethyl formamide. The reaction mixture was stirred at room temperature overnight and extracted with dichloromethane. The organic layer was washed with 10% sodium carbonate solution and water and dried (MgSO4). Solvents were removed in vacuo and the crude oil was purified by silica gel chromatography with hexane-ethyl acetate to give the corresponding phenyl-sulfide (1.9 g) as a colorless oil. This sulfide was then dissolved in 30 mL of dry dichloromethane and 3.0 g (80-85%) of 3-chloroperbenzoic acid was added in portions with stirring and occasional cooling. The reaction mixture was stirred for 2 hrs, and quenched with 10% sodium bicarbonate. The combined organic extracts were washed with aqueous sodium sulfite and brine and dried (MgSO4). The solvents was removed in vacuo and the crude oil was purified by silica gel flash chromatography using hexane-ethyl acetate to afford the pure sulfone (1.4 g) as a colorless liquid. Calcd for C15H24O3S C, 63.34; H, 8.51; S, 11.27; Found: C,63.36; H, 8.61; S, 11.23. 1.0 g N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) containing 1% trimethylchlorosilane was added to 560 mg of the above hydroxysulfone in 1 mL of anhydrous pyridine and the mixture stirred under nitrogen at 60° C. for 3 h. After evaporation of the pyridine under reduced pressure the crude product was flash chromatographed on a silica gel column with hexane followed by 9:1 hexane-ethyl acetate to give the pure hydroxy-protected sulfone (0.62 g). Calcd for C18H32O3SSI C, 60.62; H, 9.05; S 8.99 Found C, 60.73, H, 9.22; S, 8.88%, 1H NMR (CDCl3) δ 0.058 (9H,s,Si--(CH3)3) 3.07-3.12 (2H,m, 7-H) 7.57 (2H, t, J=6.8 Hz, Ar H metal) 7.65 (1 H,t, J=6.8 Hz, Ar H para) 7.92 (2H,d J=6.8 Hz,Ar H, Ortho).

1. extractionextracted with dichloromethane
2. washThe organic layer was washed with 10% sodium carbonate solution and water
3. dry with materialdried (MgSO4)
4. customSolvents were removed in vacuo
5. customthe crude oil was purified by silica gel chromatography with hexane-ethyl acetate