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

HRID 1037006Notes

Reaction equation

HRID 1037006 reaction equation
[CH3:1][C:2]1[CH:10]=[C:9]([C:11]2[CH2:15][C:14]([C:20]3[CH:25]=[C:24]([Cl:26])[C:23]([Cl:27])=[C:22]([Cl:28])[CH:21]=3)([C:16]([F:19])([F:18])[F:17])[O:13][N:12]=2)[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.[NH2:54][CH2:55][C:56]1[CH:67]=[CH:66][C:59]2[B:60]([OH:65])[O:61][C:62]([CH3:64])([CH3:63])[C:58]=2[CH:57]=1.Cl>CC#N>[OH:65][B:60]1[C:59]2[CH:66]=[CH:67][C:56]([CH2:55][NH:54][C:4](=[O:6])[C:3]3[CH:7]=[CH:8][C:9]([C:11]4[CH2:15][C:14]([C:20]5[CH:21]=[C:22]([Cl:28])[C:23]([Cl:27])=[C:24]([Cl:26])[CH:25]=5)([C:16]([F:18])([F:17])[F:19])[O:13][N:12]=4)=[CH:10][C:2]=3[CH3:1])=[CH:57][C:58]=2[C:62]([CH3:64])([CH3:63])[O:61]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 866854502-Methyl-4-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)benzoic acidHCID 86685451HCID 86685451, compound

Product 1

HCID 71575880N-((1-hydroxy-3,3-dimethyl-1,3-dihydrobenzo[c][1,2]oxaborol-5-yl)methyl)-2-methyl-4-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)benzamideYield 25.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

The solution of 2-methyl-4-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazol-3-yl)benzoic acid (300 mg, 0.665 mmol) and HATU (505.4 mg, 1.33 mmol) in CH3CN (15 mL) at rt was stirred for 5 min. The mixture was added to a solution of 5-(aminomethyl)-3,3-dimethylbenzo[c][1,2]oxaborol-1(3H)-ol hydrochloride (181.1 mg, 0.798 mmol) and TEA (268.7 mg, 2.66 mmol) in CH3CN (15 mL). Then the mixture was stirred at rt for 2 h. The solution was acidified with HCl (1 N) and extracted with EA. The combined organic layers were washed with brine, dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by prep-TLC (PE:EA=2:1) to give the final title compound (105 mg, yield 25%): 1H NMR (300 MHz, DMSO-d6): δ 9.0 (s, 1H), 8.95 (t, 1H), 7.83 (s, 2H), 7.64-7.59 (m, 3 H), 7.47 (d, 1H), 7.34-7.29 (m, 2H), 4.52-4.50 (d, 2H), 4.37-4.34 (m, 2 H), 2.38 (s, 3H), 1.44 (s, 6 H); HPLC purity: 98.1% at 220 nm and 98.8% at 254 nm; MS: m/z=625 and 627 [M+H]+.

Workup

  1. extractionextracted with EA
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by prep-TLC (PE:EA=2:1)

Sources & evidence

ORD record
ord-11bf6eb11b4e43bc82bb5411ced33a3d
Source dataset
uspto-grants-2013_10
Patent number
US08546357B2

Reaction notes

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