反应详情

To a solution of 217 mg (0.438 mmole) of 5-n-butyl-2,4-dihydro-4-[(2'-nitrobiphenyl-4-yl)methyl]-2-[2-(trifluoromethyl)phenyl]-3H-1,2,4-triazol-3-one (from Step C) in 2.2 ml of THF stirred at 0° C. under N2 was added dropwise a solution of 692 mg (3.07 mmole) of stannous chloride dihydrate in 1.2 ml of concentrated hydrochloric acid. After 15 minutes, the ice bath was removed, and the mixture was allowed to warm to room temperature. After 2 hours at room temperature, by which time TLC (98:2 CH2Cl2 --MeOH) indicated complete disappearance of starting material, the reaction mixture was added to a mixture of 10.6 g of ice, 3 ml of 50% NaOH, and 6 ml of ether. The resulting mixture was stirred at 0° C. for about 1 hour and then extracted with 2×10 ml of ether and 1×10 ml of ethyl acetate. The combined organic extracts were washed with brine, dried over sodium sulfate, filtered, and concentrated. The crude product was flash chromatographed twice on silica gel (first elution with a gradient of 0.5-5% MeOH in CH2Cl2, second elution with 0.5% MeOH in CH2Cl2). Concentration of the product fractions afforded 95 mg (47%) of the title compound as a sticky foam; satisfactory purity by TLC (98:2 CH2Cl2 --MeOH) for use in the next step; mass spectrum (FAB) m/e 467 (M+1)+.

1. customthe ice bath was removed
2. waitAfter 2 hours at room temperature
3. additionthe reaction mixture was added to a mixture of 10.6 g of ice, 3 ml of 50% NaOH, and 6 ml of ether
4. extractionextracted with 2×10 ml of ether and 1×10 ml of ethyl acetate
5. washThe combined organic extracts were washed with brine
6. dry with materialdried over sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated
9. customchromatographed twice on silica gel (
10. washfirst elution
11. washwith a gradient of 0.5-5% MeOH in CH2Cl2, second elution with 0.5% MeOH in CH2Cl2)