Water → 1-(4'-fluorophenyl)-1,3-dihydroisobenzofuran-5-ylmethanol

HRID 990281Notes

Reaction equation

HRID 990281 reaction equation
[BH4-].[Na+].[F:3][C:4]1[CH:23]=[CH:22][C:7]([C:8]([C:10]2[CH:18]=[CH:17][C:13]([C:14](O)=[O:15])=[CH:12][C:11]=2[C:19](O)=[O:20])=O)=[CH:6][CH:5]=1.S(OC)(OC)(=O)=O.O>C1COCC1>[F:3][C:4]1[CH:23]=[CH:22][C:7]([CH:8]2[C:10]3[C:11](=[CH:12][C:13]([CH2:14][OH:15])=[CH:17][CH:18]=3)[CH2:19][O:20]2)=[CH:6][CH:5]=1

Participants

6

Reactant 4

HCID 962WaterHCID 6497Dimethyl SulfateHCID 4311764Sodium borohydrideHCID 98355864-(4-Fluorobenzoyl)isophthalic acid

Product 1

HCID 99211661-(4'-fluorophenyl)-1,3-dihydroisobenzofuran-5-ylmethanolYield 86%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
55 °C

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-b220dc8c99e94259a5816044e8a4eed8
Source dataset
uspto-grants-2002_10
Patent number
US06458975B1

Reaction notes

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