反应详情

To a suspension of 5-(4-fluorophenyl)-4-(4-pyridinyl)-1H-pyrazole-3-carboxylic acid, monohydrate prepared in accordance with Example A-200 (0.526 g, 2.0 mmol) in dry THF (15 ml) at reflux under nitrogen, a solution of 1N lithium aluminum hydride in THF (4.0 ml, 4.0 mmol) was added dropwise over 15 minutes. A precipitate formed. The mixture was boiled for an additional hour. Excess lithium aluminum hydride was then decomposed by cautiously adding a solution of 4N potassium hydroxide in water (0.5 ml). Upon hydrolysis, a white salt precipitated. After the addition was complete, the mixture was heated at reflux for 15 minutes. The hot solution was filtered by suction through a Buchner funnel, and remaining product was extracted from the precipitate by refluxing with THF (15 ml) for 1 hour, followed again by suction filtration. The combined filtrates were concentrated under reduced pressure. The resulting residue was taken into ethyl acetate, washed with water and brine, dried over MgSO4 to give a crude product (0.45 g). Recrystallization of the crude product from methanol gave 5-(4-fluorophenyl)-4-(4-pyridinyl)-1H-pyrazole-3-methanol (0.2808 g, 56.5%). DSC: 260.26° C.; Anal. Calc'd for C15H12N3FO (269): C, 66.91; H, 4.49; N, 15.60; Found: C, 66.07; H, 4.63; N, 15.20. MS (MH+): 270 (base peak).

1. temperatureat reflux under nitrogen
2. customA precipitate formed
3. waitThe mixture was boiled for an additional hour
4. customUpon hydrolysis
5. customa white salt precipitated
6. additionAfter the addition
7. temperaturethe mixture was heated
8. temperatureat reflux for 15 minutes
9. filtrationThe hot solution was filtered by suction through a Buchner funnel
10. extractionwas extracted from the precipitate
11. temperatureby refluxing with THF (15 ml) for 1 hour
12. filtrationfollowed again by suction filtration
13. concentrationThe combined filtrates were concentrated under reduced pressure
14. washwashed with water and brine
15. dry with materialdried over MgSO4
16. customto give a crude product (0.45 g)
17. customRecrystallization of the crude product from methanol