反应详情

To an ice-cooled solution of approximately 33 m moles of aluminum hydride in 50 ml of tetrahydrofuran is added a solution of 6.86 g of 8-chloro-6-(2-fluoro-phenyl)-1-methyl-4-oxo-1H,6H-pyrazolo[4,3-d](2)benzoxepine in 150 ml of dry tetrahydrofuran under an atmosphere of nitrogen. After the addition, the mixture is stirred an additional 30 minutes in an ice bath. The excess of the reagent is then carefully destroyed by adding water; 50 ml of 2N hydrochloric acid is added to dissolve the voluminous precipitate. The two layers are separated, the organic layer is washed with a saturated aqueous sodium chloride solution and dried over anhydrous sodium sulfate. All aqueous layers are reextracted with diethyl ether. The residue (consisting of a mixture of thermally interconvertible isomers) is taken up in 100 ml of dioxane and refluxed for 2 hours. The dioxane is then removed under reduced pressure and the residue is crystallized from 30 ml of diethyl ether to give the thermodynamically more stable isomer of the 3-[4-chloro-2-(2-fluoro-α-hydroxy-benzyl)-phenyl]-4-hydroxymethyl-2-methyl-pyrazole, m.p. 152°-155°. The mother liquor is equilibriated again by refluxing in dioxane and an additional amount of the product, m.p. 153°-155°, can be collected.

1. additionAfter the addition
2. customThe excess of the reagent is then carefully destroyed
3. additionby adding water
4. addition50 ml of 2N hydrochloric acid is added
5. dissolutionto dissolve the voluminous precipitate
6. customThe two layers are separated
7. washthe organic layer is washed with a saturated aqueous sodium chloride solution
8. dry with materialdried over anhydrous sodium sulfate
9. additionThe residue (consisting of a mixture of thermally interconvertible isomers)
10. temperaturerefluxed for 2 hours
11. customThe dioxane is then removed under reduced pressure
12. customthe residue is crystallized from 30 ml of diethyl ether