Diisopropylethylamine → 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-6-yl)methyl)-N,2-di-ethylbenzamide

HRID 1037012Notes

Reaction equation

HRID 1037012 reaction equation
[CH3:1][C:2]1([CH3:15])[O:6][B:5]([OH:7])[C:4]2[CH:8]=C(CNC)[CH:10]=[CH:11][C:3]1=2.[Cl:16][C:17]1[CH:18]=[C:19]([C:24]2([C:39]([F:42])([F:41])[F:40])[O:28][N:27]=[C:26]([C:29]3[CH:37]=[CH:36][C:32]([C:33]([OH:35])=O)=[C:31]([CH3:38])[CH:30]=3)[CH2:25]2)[CH:20]=[C:21]([Cl:23])[CH:22]=1.F[B-](F)(F)F.Br[C:49]1C=CC=C[N+]=1CC.CC[N:59]([CH:63]([CH3:65])C)[CH:60]([CH3:62])C>C(Cl)Cl.O>[Cl:23][C:21]1[CH:20]=[C:19]([C:24]2([C:39]([F:42])([F:40])[F:41])[O:28][N:27]=[C:26]([C:29]3[CH:37]=[CH:36][C:32]([C:33]([N:59]([CH2:60][C:62]4[CH:10]=[CH:11][C:3]5[C:2]([CH3:15])([CH3:1])[O:6][B:5]([OH:7])[C:4]=5[CH:8]=4)[CH2:63][CH3:65])=[O:35])=[C:31]([CH2:38][CH3:49])[CH:30]=3)[CH2:25]2)[CH:18]=[C:17]([Cl:16])[CH:22]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 27363002-Bromo-1-ethylpyridinium tetrafluoroborateHCID 231598114-(5-(3,5-Dichlorophenyl)-5-(tri fluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acidHCID 866854591,3-dihydro-1-hydroxy-N,3,3-trimethyl-2,1-Benzoxaborole-6-methanamine

Product 1

HCID 866854614-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-N-((1-hydroxy-3,3-dimethyl-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)methyl)-N,2-di-ethylbenzamideYield 11.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a cold solution of 3,3-dimethyl-6-((methylamino)methyl)benzo[c][1,2]-oxaborol-1(3H)-ol (246 mg, 1.2 mmol), 4-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid (502 mg, 1.2 mmol) and 2-bromo-1-ethylpyridinium tetrafluoroborate (BEP) (292 mg, 1.32 mmol) in DCM (10 mL) was added DIPEA (464 mg, 3.6 mmol). The reaction mixture was stirred at rt overnight. Water (20 mL) was added and the mixture was extracted three times with ethyl acetate. The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by prep-HPLC to give 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-6-yl)methyl)-N,2-di-ethylbenzamide (84 mg; yield 11.6%) as a white solid. HPLC purity: 98.30% at 220 nm and 98.87% at 254 nm; MS: m/z=604.9 (M+1, ESI+).

Workup

  1. extractionthe mixture was extracted three times with ethyl acetate
  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 by prep-HPLC

Sources & evidence

ORD record
ord-9044aeddc48849fc82fb9768e7b7a804
Source dataset
uspto-grants-2013_10
Patent number
US08546357B2

Reaction notes

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