Isopropanol → 6-Fluoro-3-(4-methoxyphenyl)-1,2-benzisoxazole

HRID 852074Notes

Reaction equation

HRID 852074 reaction equation
F[C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([C:12]1[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=1)=[N:10][OH:11].C(O)(C)C.[OH-].[K+]>O>[F:8][C:6]1[CH:5]=[CH:4][C:3]2[C:9]([C:12]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=3)=[N:10][O:11][C:2]=2[CH:7]=1

Participants

5

Reactant 3

HCID 3776IsopropanolHCID 14797Potassium HydroxideHCID 72465828HCID 72465828, compound

Product 1

HCID 179063296-Fluoro-3-(4-methoxyphenyl)-1,2-benzisoxazoleYield 73%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

Combine (2,4-difluoro-phenyl)-(4-methoxy-phenyl)-methanone oxime (277.5 g, 1.05 mol), water (200 mL) and isopropyl alcohol (1140 mL) and heat (˜75-80° C.) under a nitrogen atmosphere. Add 45% potassium hydroxide (591.5 g), in one portion, followed by water (75 mL). Immediate exotherm to 82° C. Continue heating for 5.3 hours. Cool reaction mixture to room temperature overnight. Cool reaction mixture in an ice bath, filter and wash (2×250 mL) filter cake with a cold mixture of isopropyl alcohol and water (20:80). Let filter cake dry to the air to give the title compound (182.7 g, 73% Yield): 1H NMR (CDCl3, 200 MHz) δ 3.9 (s, 3H), 7.1 (m, 3H), 7.3 (m, 1H), 7.85 (m, 3H). Purity by LC/MS (APCl)=100% area, [M+H]+=244 m/e.

Workup

  1. customto 82° C
  2. temperatureContinue heating for 5.3 hours
  3. temperatureCool
  4. customreaction mixture to room temperature overnight
  5. temperatureCool
  6. customreaction mixture in an ice bath
  7. filtrationfilter
  8. washwash (2×250 mL)
  9. filtrationfilter cake
  10. additionwith a cold mixture of isopropyl alcohol and water (20:80)
  11. filtrationLet filter cake
  12. customdry to the air

Sources & evidence

ORD record
ord-a2fdcc04ea7e4333bde9acdeb8368e38
Source dataset
uspto-grants-2007_08
Patent number
US07253165B2

Reaction notes

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