Diisopropylamine → HCID 76765796, compound

HRID 69398Notes

Reaction equation

HRID 69398 reaction equation
[CH2:1]([NH:5][C:6](=[O:31])[C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH2:17][C:16]([C:22]3[CH:27]=[C:26]([Cl:28])[CH:25]=[C:24]([Cl:29])[CH:23]=3)([C:18]([F:21])([F:20])[F:19])[O:15][N:14]=2)=[CH:9][C:8]=1[CH3:30])[CH2:2][CH2:3][CH3:4].C(NC(C)C)(C)C.C([Li])CCC>O1CCCC1>[CH2:1]([NH:5][C:6](=[O:31])[C:7]1[CH:12]=[CH:11][C:10]([C:13](=[N:14][OH:15])[CH:17]=[C:16]([C:22]2[CH:27]=[C:26]([Cl:28])[CH:25]=[C:24]([Cl:29])[CH:23]=2)[C:18]([F:19])([F:21])[F:20])=[CH:9][C:8]=1[CH3:30])[CH2:2][CH2:3][CH3:4]

Participants

5

Reactant 3

HCID 7912DiisopropylamineHCID 67295194HCID 67295194, compoundHCID 178418339Butyllithium

Product 1

HCID 76765796HCID 76765796, compoundYield 70%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of N-butyl-4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzamide (made as described in EP 1,731,512) (1670 mg, 4.13 mmol) and N,N-diisopropylamine (880 mg, 8.69 mmol) in dry tetrahydrofuran (10 ml) was added n-butyl lithium (“n-BuLi”) (1.55M in hexane) (5.6 ml, 8.69 mmol) at −90° C. The reaction mixture was allowed to warm to 0° C. over a period of 2 hours and quenched by addition of aqueous ammonium chloride (saturated). The mixture was extracted several times with diethyl ether. The combined organic extracts were dried over magnesium sulfate and concentrated. The residue was purified by chromatography on silica gel (eluent: hexane/ethyl acetate 2:1) to give N-butyl-4-[3-(3,5-dichloro-phenyl)-4,4,4-trifluoro-1-hydroxyimino-but-2-enyl]-2-methyl-benzamide (1180 mg, 70% yield) as a yellow resin. 1H-NMR (CDCl3, 300 MHz): 8.52 (bs, 1H), 7.45-7.36 (m, 6H), 6.75 (s, 1H), 5.81 (m, 1H), 3.46-3.43 (m, 2H), 2.47 (s, 3H), 1.54-1.39 (m, 4H), 0.97 (t, 3H) ppm.

Workup

  1. customquenched by addition of aqueous ammonium chloride (saturated)
  2. extractionThe mixture was extracted several times with diethyl ether
  3. dry with materialThe combined organic extracts were dried over magnesium sulfate
  4. concentrationconcentrated
  5. customThe residue was purified by chromatography on silica gel (eluent: hexane/ethyl acetate 2:1)

Sources & evidence

ORD record
ord-e244720a0e774435a15b3bc3d2ca2a8c
Source dataset
uspto-grants-2014_09
Patent number
US08822502B2

Reaction notes

Loading…