Ethyl Acetate → 5-(5-(3-chloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-3,3-dimethylbenzo[c][1,2]oxaborol-1(3H)-ol

HRID 1750798Notes

Reaction equation

HRID 1750798 reaction equation
[OH:1]/[N:2]=[C:3](\Cl)/[C:4]1[CH:15]=[CH:14][C:7]2[B:8]([OH:13])[O:9][C:10]([CH3:12])([CH3:11])[C:6]=2[CH:5]=1.[Cl:17][C:18]1[CH:23]=[C:22]([C:24]([C:26]([F:29])([F:28])[F:27])=[CH2:25])[CH:21]=[CH:20][C:19]=1[F:30].CC(=O)OCC>CN(C=O)C>[Cl:17][C:18]1[CH:23]=[C:22]([C:24]2([C:26]([F:29])([F:27])[F:28])[O:1][N:2]=[C:3]([C:4]3[CH:15]=[CH:14][C:7]4[B:8]([OH:13])[O:9][C:10]([CH3:12])([CH3:11])[C:6]=4[CH:5]=3)[CH2:25]2)[CH:21]=[CH:20][C:19]=1[F:30]

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 668238852-Chloro-1-fluoro-4-(3,3,3-trifluoroprop-1-en-2-yl)benzeneHCID 140608106(5Z)-N,1-dihydroxy-3,3-dimethyl-2,1-benzoxaborole-5-carboximidoyl chloride

Product 1

HCID 715717925-(5-(3-chloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-3,3-dimethylbenzo[c][1,2]oxaborol-1(3H)-olYield 32.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (Z)—N,1-dihydroxy-3,3-dimethyl-1,3-dihydrobenzo[c][1,2]oxaborole-5-carbimidoyl chloride (239 mg, 1.0 mmol) and 2-chloro-1-fluoro-4-(3,3,3-trifluoroprop-1-en-2-yl)benzene (240 mg, 1.07 mmol) in DMF (5 mL) at rt was added TEA (108 mg, 1.07 mmol). The reaction mixture was stirred at rt for 18 h, poured into ice-water and extracted with EA (20 mL). The organic layer was washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography over silica gel eluted with PE:EA (6:1) to give the final title compound 5-(5-(3-chloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-3,3-dimethylbenzo[c][1,2]oxaborol-1(3H)-ol (140 mg; yield 30.6%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 9.21 (s, 1H), 7.80-7.70 (m, 4H), 7.64-7.60 (m, 2H), 4.43 (d, J=18.4 Hz, 1H), 4.27 (d, J=18.4 Hz, 1H), 1.48 (s,6H) ppm; HPLC purity: 96.0% at 220 nm and 96.4% at 254 nm; MS: m/z=428.1 (M+, ESI+).

Workup

  1. extractionextracted with EA (20 mL)
  2. washThe organic layer was washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by column chromatography over silica gel
  7. washeluted with PE

Sources & evidence

ORD record
ord-e5016540164a4aa79d7f170b9592bc74
Source dataset
uspto-grants-2015_10
Patent number
US09156860B2

Reaction notes

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