Sodium Hydroxide → 3-(4-Bromo-5-methyl-thiophen-2-yl)-5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazole

HRID 68567

Reaction equation

HRID 68567 reaction equation
Cl.[NH2:2][OH:3].[OH-].[Na+].[Br:6][C:7]1[CH:8]=[C:9]([C:13](=O)[CH:14]=[C:15]([C:20]2[CH:25]=[C:24]([Cl:26])[CH:23]=[C:22]([Cl:27])[CH:21]=2)[C:16]([F:19])([F:18])[F:17])[S:10][C:11]=1[CH3:12]>CCO>[Br:6][C:7]1[CH:8]=[C:9]([C:13]2[CH2:14][C:15]([C:20]3[CH:25]=[C:24]([Cl:26])[CH:23]=[C:22]([Cl:27])[CH:21]=3)([C:16]([F:19])([F:18])[F:17])[O:3][N:2]=2)[S:10][C:11]=1[CH3:12]

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 443297Hydroxyamine hydrochlorideHCID 867066471-(4-Bromo-5-methyl-thiophen-2-yl)-3-(3,5-dichloro-phenyl)-4,4,4-trifluoro-but-2-en-1-one

Product 1

HCID 867066483-(4-Bromo-5-methyl-thiophen-2-yl)-5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazoleYield 54.7%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Hydroxylamine hydrochloride (13 g) and NaOH (18 g) are added to a solution of 1-(4-bromo-5-methyl-thiophen-2-yl)-3-(3,5-dichloro-phenyl)-4,4,4-trifluoro-but-2-en-1-one (84 g, 71% purity) in EtOH (1000 ml) at room temperature. After 12 hours at room, the reaction mixture is concentrated in vacuo, diluted with diethylether and water. The aqueous phase is separated and further extracted two times with diethylether. The organic phases are combined, washed with a saturated aqueous solution of NaCl, dried over MgSO4 and concentrated in vacuo. The crude product is purified by chromatography on silica gel (1800 g) eluting with a mixture of heptane and dichloromethane (4:1) to yield 3-(4-bromo-5-methyl-thiophen-2-yl)-5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazole (47 g) as a light brown crystals.

Workup

  1. concentrationthe reaction mixture is concentrated in vacuo
  2. additiondiluted with diethylether and water
  3. customThe aqueous phase is separated
  4. extractionfurther extracted two times with diethylether
  5. washwashed with a saturated aqueous solution of NaCl
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated in vacuo
  8. customThe crude product is purified by chromatography on silica gel (1800 g)
  9. washeluting with a mixture of heptane and dichloromethane (4:1)

Sources & evidence

ORD record
ord-66a2043a24c04fb2af37d9d8c8b07f9a
Source dataset
uspto-grants-2014_09
Patent number
US08822466B2

Linked notes

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