反应详情

A solution of methyl 3-[1-(4-chlorobenzyl)-3-(1,1-dimethylethylthio)-5-(pyrid-2-ylmethoxy)indol-2-yl]-2,2-dimethylpropionate (8.8 g; 16 mmol), prepared as in step 5, in 100 mL 1:2:1 THF, methanol, 1N aqueous LiOH was heated at reflux for 3 hours. The reaction mixture was concentrated, diluted with water, and acidified to pH 5-6 with solid citric acid. The mixture was extracted with ethyl acetate. The extracts were dried over magnesium sulfate and the solvent was evaporated. The product was recrystallized from ethyl acetate/hexane to give 3-[1-(4-chlorobenzyl)-3-(1,1-dimethylethylthio)-5-(pyrid-2-ylmethoxy)indol-2-yl]-2,2-dimethylpropionic acid as a white solid. m.p. 189°-190° C. 1H NMR (300 MHz, DMSO-d6) δ1.09 (s, 6H), 1.10 (s, 9H), 3.18 (bs, 2H), 5.20 (s, 2H), 5.47 (s, 2H), 6.85 (m, 3H), 7.09 (d, J=3 Hz, 1H), 7.32 (m, 4H), 7.49 (d, J=8 Hz, 1H), 7.79 (m, 1H), 8.57 (m, 1H). MS (DCI/NH3) 537 (M+H)+. Analysis calcd for C30H33ClN2O3S; C, 67.08; H, 6.19; N, 5.22. Found: C, 67.30; H, 6.21; N, 5.18.

1. temperatureat reflux for 3 hours
2. concentrationThe reaction mixture was concentrated
3. additiondiluted with water
4. extractionThe mixture was extracted with ethyl acetate
5. dry with materialThe extracts were dried over magnesium sulfate
6. customthe solvent was evaporated
7. customThe product was recrystallized from ethyl acetate/hexane