Methanol → HCID 136158584, compound

HRID 852075Notes

Reaction equation

HRID 852075 reaction equation
B(Br)(Br)Br.[F:5][C:6]1[CH:22]=[CH:21][C:9]2[C:10]([C:13]3[CH:18]=[CH:17][C:16]([O:19]C)=[CH:15][CH:14]=3)=[N:11][O:12][C:8]=2[CH:7]=1.CO>ClCCl.C(O)(C)C>[F:5][C:6]1[CH:22]=[CH:21][C:9]2[C:10]([C:13]3[CH:14]=[CH:15][C:16]([OH:19])=[CH:17][CH:18]=3)=[N:11][O:12][C:8]=2[CH:7]=1

Participants

6

Reactant 3

HCID 887MethanolHCID 25134Boron tribromideHCID 179063296-Fluoro-3-(4-methoxyphenyl)-1,2-benzisoxazole

Product 1

HCID 136158584HCID 136158584, compoundYield 83.4%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 6344DichloromethaneSolvent2×

Procedure

Add a 1.0 M solution of boron tribromide (2.31 L, 2.31 mol) in dichloromethane (1.87 L) to a cold (0° C.) solution of 6-fluoro-3-(4-methoxy-phenyl)-benzo[d]isoxazole (187.2 g, 0.77 mol) in dichloromethane, over ˜2 hours. Warm to room temperature overnight. Cool reaction mixture to ˜3° C. and add methanol (4 L) over a period of time of 1 hour, keeping the temperature of the reaction mixture at 3-10° C. Gas evolution occurs. Concentrate (40-50° C., 50 torr) reaction mixture to give a gray solid. Heat to dissolve the gray solid in isopropyl alcohol (550 mL) at reflux. Cool (room temperature), followed by 0-5° C. for 1 hour. Filter off the solid and wash filter cake with cold (0° C.) isopropyl alcohol (265 mL) and dry to air. Subsequently dry the solid in the oven (60° C., 50 torr) overnight to give the title compound (147.2 g, 83% Yield): 1H NMR (DMSO-d6, 200 MHz) δ 7.0 (d, 2H), 7.4 (t, 1H), 7.8 (d, 1H), 7.84 (d, 2H), 8.18 (m, 1H). Purity by LC/MS (APCl)=100% area, [M+H]+=230 m/e.

Workup

  1. temperatureCool
  2. customreaction mixture to ˜3° C.
  3. customat 3-10° C
  4. concentrationConcentrate
  5. custom(40-50° C., 50 torr) reaction mixture
  6. customto give a gray solid
  7. temperatureHeat
  8. temperatureat reflux
  9. temperatureCool (room temperature)
  10. waitfollowed by 0-5° C. for 1 hour
  11. filtrationFilter off the solid
  12. washwash
  13. filtrationfilter cake with cold (0° C.) isopropyl alcohol (265 mL)
  14. customdry to air
  15. customSubsequently dry the solid in the oven (60° C., 50 torr) overnight

Sources & evidence

ORD record
ord-68b4ffd2ccfa461ab2f885409ea8b87c
Source dataset
uspto-grants-2007_08
Patent number
US07253165B2

Reaction notes

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