Sodium Hydroxide → 5-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-3-methyl thiophene-2-carboxylic acid (2,2,2-trifluoro-ethyl)-amide

HRID 242397Notes

Reaction equation

HRID 242397 reaction equation
[O-]Cl.[Na+].[OH-].[Na+].[F:6][C:7]([F:22])([F:21])[CH2:8][NH:9][C:10]([C:12]1[S:13][C:14]([CH:18]=[N:19][OH:20])=[CH:15][C:16]=1[CH3:17])=[O:11].[Cl:23][C:24]1[CH:29]=[C:28]([C:30]([C:32]([F:35])([F:34])[F:33])=[CH2:31])[CH:27]=[C:26]([Cl:36])[CH:25]=1>C1COCC1.C(OCC)C>[F:22][C:7]([F:6])([F:21])[CH2:8][NH:9][C:10]([C:12]1[S:13][C:14]([C:18]2[CH2:31][C:30]([C:28]3[CH:27]=[C:26]([Cl:36])[CH:25]=[C:24]([Cl:23])[CH:29]=3)([C:32]([F:33])([F:35])[F:34])[O:20][N:19]=2)=[CH:15][C:16]=1[CH3:17])=[O:11]

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 231598231,3-Dichloro-5-(3,3,3-trifluoroprop-1-en-2-yl)benzeneHCID 23665760Sodium HypochloriteHCID 866580365-(Hydroxyimino-methyl)-3-methyl-thiophene-2-carboxylic acid (2,2,2-trifluoro-ethyl)-amide

Product 1

HCID 866580375-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-3-methyl thiophene-2-carboxylic acid (2,2,2-trifluoro-ethyl)-amideYield 15.7%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

Chlorox (4%, 1.02 ml) and NaOH (1N, 0.1 ml) are premixed and then added to a solution of 5-(hydroxyimino-methyl)-3-methyl-thiophene-2-carboxylic acid (2,2,2-trifluoro-ethyl)-amide (200 mg) and 1,3-dichloro-5-(1-trifluoromethyl-vinyl)-benzene (170 mg, example 1, Step A) in THF (3 ml) and diethyl ether (3 ml) at 5° C. The cold bath is then removed. After 21 hours, water is added and the reaction mixture is extracted three times with ethyl acetate. The organic phases are combined, dried over Na2SO4 and concentrated in vacuo. The crude product is purified on a semi-preparative HPLC to yield 5-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-3-methyl-thiophene-2-carboxylic acid (2,2,2-trifluoro-ethyl)-amide (56 mg) as light yellow oil. MS (HPLC/MS): 505 (MH+). Retention time: 4.38 min.

Workup

  1. customThe cold bath is then removed
  2. additionwater is added
  3. extractionthe reaction mixture is extracted three times with ethyl acetate
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe crude product is purified on a semi-preparative HPLC

Sources & evidence

ORD record
ord-269693ba04244e8d850bec9ae1a1caa6
Source dataset
uspto-grants-2014_02
Patent number
US08653116B2

Reaction notes

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