Boron tribromide → 1-(4-{4-[3-(4-Fluoro-phenyl)-5-hydroxymethyl-isoxazol-4-yl]-imidazol-1-yl}-phenyl)-ethanone

HRID 2219414Notes

Reaction equation

HRID 2219414 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]([C:13]3[N:14]=[CH:15][N:16]([C:18]4[CH:23]=[CH:22][C:21]([C:24](=[O:26])[CH3:25])=[CH:20][CH:19]=4)[CH:17]=3)=[C:11]([CH2:27][O:28]C)[O:10][N:9]=2)=[CH:4][CH:3]=1.B(Br)(Br)Br>ClCCl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]([C:13]3[N:14]=[CH:15][N:16]([C:18]4[CH:23]=[CH:22][C:21]([C:24](=[O:26])[CH3:25])=[CH:20][CH:19]=4)[CH:17]=3)=[C:11]([CH2:27][OH:28])[O:10][N:9]=2)=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 25134Boron tribromideHCID 67420992HCID 67420992, compound

Product 1

HCID 674206471-(4-{4-[3-(4-Fluoro-phenyl)-5-hydroxymethyl-isoxazol-4-yl]-imidazol-1-yl}-phenyl)-ethanoneYield 15.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

To a stirred solution of 1-(4-{4-[3-(4-fluoro-phenyl)-5-methoxymethyl-isoxazol-4-yl]-imidazol-1-yl}-phenyl)-ethanone (239 mg, 0.61 mmol) in dry dichloromethane (4 mL) was added slowly boron tribromide (0.17 mL, 0.3 mmol) at dry ice-acetone bath cooling temperature. After complete addition, the resulting mixture was stirred at −78° C. for 15 min, and −15° C. for 35 min, and then allowed to warm up to room temperature for 20 min. The reaction was quenched with saturated sodium bicarbonate (30 mL). The organic layer was separated, and the aqueous phase was extracted with dichloromethane and ethylacetate. The combined organic extracts were then dried over sodium sulphate and evaporated. Purification by preparative HPLC afforded the title compound (35 mg, 15%) which was obtained as an off-white solid. MS: m/e=378.0 [M+H]+.

Workup

  1. temperaturecooling temperature
  2. additionAfter complete addition
  3. wait−15° C. for 35 min
  4. temperatureto warm up to room temperature for 20 min
  5. customThe reaction was quenched with saturated sodium bicarbonate (30 mL)
  6. customThe organic layer was separated
  7. extractionthe aqueous phase was extracted with dichloromethane and ethylacetate
  8. dry with materialThe combined organic extracts were then dried over sodium sulphate
  9. customevaporated
  10. customPurification by preparative HPLC

Sources & evidence

ORD record
ord-90c04bd604cd43ea968769424e82795e
Source dataset
uspto-grants-2008_08
Patent number
US07414061B2

Reaction notes

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