反应详情

温度

55 °C

To a suspension of sodium borohydride (15.0 g) dispersed in THF (130 ml) was added dropwise at 20-30° C. a solution of 4-(4′-fluorobenzoyl)isophthalic acid (26.0 g) synthesized in Example 4 in THF (260 ml) and the mixture was heated to 55° C. Dimethyl sulfate (51.0 g) was added dropwise at 55-65° C. After the dropwise addition, the mixture was refluxed for 5 hr, and hydrolyzed with water (130 ml) in an ice bath. THF was evaporated under reduced pressure. To the residue was added 85% phosphoric acid (52 g) and the mixture was stirred at 60° C. for 5 hr. Water (390 ml) was added and the mixture was cooled. The generated crystals were collected by filtration, washed with water and dried to give crude 1-(4′-fluorophenyl)-1,3-dihydroisobenzofuran-5-ylmethanol (20.4 g). This was recrystallized from a mixed solvent of ethyl acetate and heptane (2:3) to give nearly pure 1-(4′-fluorophenyl)-1,3-dihydroisobenzofuran-5-ylmethanol (18.9 g, 86%). The various spectrum data of the crystals were the same as those obtained in Example 12.

1. additionAfter the dropwise addition
2. temperaturethe mixture was refluxed for 5 hr
3. customTHF was evaporated under reduced pressure
4. additionTo the residue was added 85% phosphoric acid (52 g)
5. additionWater (390 ml) was added
6. temperaturethe mixture was cooled
7. filtrationThe generated crystals were collected by filtration
8. washwashed with water
9. customdried
10. customto give crude 1-(4′-fluorophenyl)-1,3-dihydroisobenzofuran-5-ylmethanol (20.4 g)
11. customThis was recrystallized from a mixed solvent of ethyl acetate and heptane (2:3)