Hydrochloric Acid → 5-(5-(4-fluoro-3-(trifluoromethyl)phenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-3,3-dimethylbenzo[c][1,2]oxaborol-1(3H)-ol

HRID 532190Notes

Reaction equation

HRID 532190 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.[F:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]([C:26]([F:29])([F:28])[F:27])=[CH2:25])=[CH:20][C:19]=1[C:30]([F:33])([F:32])[F:31].Cl.CC(=O)OCC>CN(C=O)C>[F:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]2([C:26]([F:27])([F:28])[F:29])[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:20][C:19]=1[C:30]([F:31])([F:32])[F:33]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 866850651-Fluoro-2-(trifluoromethyl)-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 715719015-(5-(4-fluoro-3-(trifluoromethyl)phenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-3,3-dimethylbenzo[c][1,2]oxaborol-1(3H)-olYield 20%

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 (522 mg, 2.18 mmol) in DMF (5 mL) was successively added 1-fluoro-2-(trifluoromethyl)-4-(3,3,3-trifluoroprop-1-en-2-yl)benzene (563 mg, 2.18 mmol) and TEA (440 mg, 4.36 mmol) below −10° C. The mixture was stirred at rt overnight, poured into 1N HCl solution and extracted with EA (30 mL×3). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by pre-TLC eluted with PE:EA (1:1, 1% HOAc) and pre-HPLC to give the final title compound (200 mg, yield 20.0%) as white solid: 1H NMR (300 MHz, DMSO-d6): δ 9.20 (s, 1H), 8.03-8.00 (m, 1H), 7.91-7.89 (d, J=12 Hz, 1H), 7.77-7.68 (m, 4H), 4.52-4.46 (d, J=18 Hz, 1H), 4.36-4.30 (d, J=18 Hz, 1H), 1.48 (s, 6H). LC-MS: 462 [M+H]+.

Workup

  1. extractionextracted with EA (30 mL×3)
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified
  7. washby pre-TLC eluted with PE

Sources & evidence

ORD record
ord-fc902a8377b04a8199662ecc972176e1
Source dataset
uspto-grants-2014_10
Patent number
US08853186B2

Reaction notes

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