Dimethylformamide → HCID 14348786, compound

HRID 414355Notes

Reaction equation

HRID 414355 reaction equation
[Cl:1][C:2]1[C:7]2[C:8]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[F:17])=[N:9][O:10][C:6]=2[CH:5]=[C:4]([OH:18])[CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH2:25](Br)[CH:26]=[CH2:27].CN(C=O)C>O>[CH2:27]([O:18][C:4]1[CH:3]=[C:2]([Cl:1])[C:7]2[C:8]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[F:17])=[N:9][O:10][C:6]=2[CH:5]=1)[CH:26]=[CH2:25]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 7841Allyl bromideHCID 11430Potassium CarbonateHCID 135583514HCID 135583514, compound

Product 1

HCID 14348786HCID 14348786, compoundYield 99.2%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 4-chloro-3-(2-fluorophenyl)-6-hydroxy-1,2-benzisoxazole (7.7 g), potassium carbonate (7.1 g), allyl bromide (6.0 g) and DMF (100 ml) was stirred at 50°-60° C. for 3 hours. After cooling the mixture, water was added and the mixture was extracted with ether. The ether layer was washed with water and dried, and the solvent was distilled off to obtain 8.8 g of 6-allyloxy-4-chloro-3-(2-fluorophenyl)-1,2-benzisoxazole. This compound (8.8 g) was refluxed in 100 ml of aniline for 3.5 hours. After cooling the mixture, concentrated hydrochloric acid and then water were added and the mixture was extracted with ether. The ether layer was washed with water and dried. After distilling off the solvent, the residue was purified by column chromatography using 1% methanol/methylene chloride as an eluant, and 6.3 g of 7-allyl-4-chloro-3-(2-fluorophenyl)-6-hydroxy-1,2-benzisoxazole (m.p. 211°-212° C.) was obtained. This compound (6.4 g) was dissolved in 300 ml of methylene chloride and 10.2 g of m-chloroperbenzoic acid was slowly added to the solution while it was stirred and cooled, and the stirring was continued for 3 hours. After cooling, water and then 50 ml of a 2N sodium hydroxide aqueous solution were added to the mixture, which was extracted with methylene chloride. The mehtylene chloride layer was washed with water and dried, then the solvent was distilled off to yield 5 g of 4-chloro-7,8-dihydro-3-(2-fluorophenyl)furo[2,3-g]-1,2-benzisoxazole-7-methanol. m.p. 109.5°-111° C. This compound exhibited a mass spectrum having a molecular ion peak at m/e 319.

Workup

  1. additionwas added
  2. extractionthe mixture was extracted with ether
  3. washThe ether layer was washed with water
  4. customdried
  5. distillationthe solvent was distilled off

Sources & evidence

ORD record
ord-9ca85f5f57504b8baf890ccbc85dc50c
Source dataset
uspto-grants-1988_12
Patent number
US04791209

Reaction notes

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