Hydrochloric Acid → 4-(5-(3,5-Dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-N-((1-hydroxy-3,3-dimethyl-1,3-dihydrobenzo[c][1,2]oxaborol-5-yl)methyl)-2-methylbenzamide

HRID 1037007Notes

Reaction equation

HRID 1037007 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([C:24]([F:27])([F:26])[F:25])[O:13][N:12]=[C:11]([C:14]3[CH:22]=[CH:21][C:17]([C:18]([OH:20])=O)=[C:16]([CH3:23])[CH:15]=3)[CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1.CCN(CC)CC.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.[NH2:60][CH2:61][C:62]1[CH:73]=[CH:72][C:65]2[B:66]([OH:71])[O:67][C:68]([CH3:70])([CH3:69])[C:64]=2[CH:63]=1.Cl>C(#N)C.CC(=O)OCC>[Cl:8][C:6]1[CH:5]=[C:4]([C:9]2([C:24]([F:26])([F:27])[F:25])[O:13][N:12]=[C:11]([C:14]3[CH:22]=[CH:21][C:17]([C:18]([NH:60][CH2:61][C:62]4[CH:73]=[CH:72][C:65]5[B:66]([OH:71])[O:67][C:68]([CH3:70])([CH3:69])[C:64]=5[CH:63]=4)=[O:20])=[C:16]([CH3:23])[CH:15]=3)[CH2:10]2)[CH:3]=[C:2]([Cl:1])[CH:7]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 231598114-(5-(3,5-Dichlorophenyl)-5-(tri fluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acidHCID 86685451HCID 86685451, compound

Product 1

HCID 715758814-(5-(3,5-Dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-N-((1-hydroxy-3,3-dimethyl-1,3-dihydrobenzo[c][1,2]oxaborol-5-yl)methyl)-2-methylbenzamideYield 18.8%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateCatalystHCID 6342AcetonitrileSolvent

Procedure

To a solution of 4-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid (300 mg, 0.72 mmol) in acetonitrile (5 ml) at 0° C. was added Et3N (291.1 mg, 2.88 mmol), HATU (546.76 mg, 1.44 mmol) and 5-(aminomethyl)-3,3-dimethylbenzo[c][1,2]oxaborol-1(3H)-ol hydrochloride (194.2 mg, 0.86 mmol). The reaction mixture was stirred overnight at rt. The mixture was poured into 1N HCl solution and extracted with EA (20 ml×3). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by prep-TLC eluted with PE:EA (1:1 with 2 drops of HOAc) and prep-HPLC to give the final title compound (80 mg, yield 18.8%) as white solid: 1H NMR (300 MHz, DMSO-d6): δ 8.99 (s, 1H), 8.95 (m, 1H), 7.81-7.82 (m, 1H), 7.62-7.64 (m, 5H), 7.49-7.60 (m, 1H), 7.29-7.46 (m, 2H) 4.50-4.52 (d, J=6.0 Hz, 2H), 4.33-4.36 (m, J=9 Hz, 2H), 2.42 (s, 3H), 1.20 (s, 6H); HPLC purity: 97.1% at 214 nm and 98.3% at 254 nm; MS: 591 [M+H]+.

Workup

  1. extractionextracted with EA (20 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 prep-TLC eluted with PE

Sources & evidence

ORD record
ord-4aa45a61f0d04249a1224878c3bac9c7
Source dataset
uspto-grants-2013_10
Patent number
US08546357B2

Reaction notes

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