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

HRID 2304020Notes

Reaction equation

HRID 2304020 reaction equation
[BH4-].[Na+].B(OC)(OC)OC.[F:10][C:11]1[CH:30]=[CH:29][C:14]([C:15]([C:17]2[CH:25]=[CH:24][C:20]([C:21](O)=[O:22])=[CH:19][C:18]=2[C:26](O)=[O:27])=O)=[CH:13][CH:12]=1.O>C1COCC1>[F:10][C:11]1[CH:30]=[CH:29][C:14]([CH:15]2[C:17]3[C:18](=[CH:19][C:20]([CH2:21][OH:22])=[CH:24][CH:25]=3)[CH2:26][O:27]2)=[CH:13][CH:12]=1

Participants

6

Reactant 4

HCID 962WaterHCID 8470Trimethyl borateHCID 4311764Sodium borohydrideHCID 98355864-(4-Fluorobenzoyl)isophthalic acid

Product 1

HCID 99211661-(4'-fluorophenyl)-1,3-dihydroisobenzofuran-5-ylmethanolYield 81%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
35 °C

Procedure

To a suspension of sodium borohydride (43.5 g) dispersed in THF (327 ml) was added trimethyl borate (9.1 g) and added dropwise at 20-30° C. a solution of 4-(4′-fluorobenzoyl)isophthalic acid (100.5 g) synthesized in Example 4 in THF (313 ml), and the mixture was heated to 35° C. A boron trifluoride-THF complex (181.7 g) was added dropwise at 35-42° C. After the dropwise addition, the mixture was heated at 40-50° C. for 7 hr, and hydrolyzed with water (101 ml) in an ice bath. THF was evaporated under reduced pressure. To the residue was added 30% sulfuric acid (110 g) and the mixture was stirred at 60° C. for 5 hr. A 25% aqueous solution of sodium hydroxide (200 g) was added and the mixture was extracted with hot toluene (450 ml) at 70° C. The hot toluene layer was washed with warm water (70° C., 60 ml), heptane (450 ml) was added and the mixture was cooled. The precipitated crystals were collected by filtration and dried to give 1-(4′-fluorophenyl)-1,3-dihydroisobenzofuran-5-ylmethanol (69.0 g, 81%). The various spectrum data of the crystals were the same as those obtained in Example 12.

Workup

  1. additionA boron trifluoride-THF complex (181.7 g) was added dropwise at 35-42° C
  2. additionAfter the dropwise addition
  3. temperaturethe mixture was heated at 40-50° C. for 7 hr
  4. customTHF was evaporated under reduced pressure
  5. additionTo the residue was added 30% sulfuric acid (110 g)
  6. additionA 25% aqueous solution of sodium hydroxide (200 g) was added
  7. extractionthe mixture was extracted with hot toluene (450 ml) at 70° C
  8. washThe hot toluene layer was washed with warm water (70° C., 60 ml), heptane (450 ml)
  9. additionwas added
  10. temperaturethe mixture was cooled
  11. filtrationThe precipitated crystals were collected by filtration
  12. customdried

Sources & evidence

ORD record
ord-f4b19f314135436d9d0af06ec27c19e3
Source dataset
uspto-grants-2002_08
Patent number
US06433196B1

Reaction notes

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