反应详情

N,N′-Carbonyldiimidazole (71 mg, 0.441 mmol) was added to a solution of 2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)pyrrolidin-2-yl)methoxy)acetic acid (acid unit S27) (150 mg, 0.420 mmol) in methylene chloride (7 ml) and the mixture was stirred for 1 h at room temperature. A solution of 4-(pyridin-3-yl)piperidin-4-ol (A2) (74 mg, 0.420 mmol) in methylene chloride (3 ml) was subsequently added and the reaction mixture was stirred for 15 h at room temperature. Thereafter, saturated sodium bicarbonate solution (10 ml) was added to the reaction mixture and the aqueous phase was subsequently extracted with methylene chloride (2×10 ml). The combined organic phases were extracted with saturated sodium chloride solution (10 ml), dried with sodium sulfate and concentrated in vacuo. The crude product was purified by flash chromatography with ethyl acetate/methanol/hexane (10:1:1). 1-(4-Hydroxy-4-(pyridin-3-yl)piperidin-1-yl)-2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)pyrrolidin-2-yl)methoxy)ethanone (160 mg, 0.309 mmol) was dissolved in methyl ethyl ketone/diethyl ether (1:1; 5 ml), and chlorotrimethylsilane (59 μl, 0.464 mmol) was slowly added. Diethyl ether (10 ml) was subsequently added and the mixture was stirred for 1 h at 0° C. The precipitate formed was filtered off, dried with exclusion of air and washed with diethyl ether.

1. stirringthe reaction mixture was stirred for 15 h at room temperature
2. extractionthe aqueous phase was subsequently extracted with methylene chloride (2×10 ml)
3. extractionThe combined organic phases were extracted with saturated sodium chloride solution (10 ml)
4. dry with materialdried with sodium sulfate
5. concentrationconcentrated in vacuo
6. customThe crude product was purified by flash chromatography with ethyl acetate/methanol/hexane (10:1:1)
7. stirringthe mixture was stirred for 1 h at 0° C
8. customThe precipitate formed
9. filtrationwas filtered off
10. customdried with exclusion of air
11. washwashed with diethyl ether