Hydrochloric Acid → 5-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-3-methyl-thiophene-2-carboxylic acid

HRID 242405Notes

Reaction equation

[Li+].[OH-].C([O:5][C:6]([C:8]1[S:9][C:10]([C:14]2[CH2:18][C:17]([C:23]3[CH:28]=[C:27]([Cl:29])[CH:26]=[C:25]([Cl:30])[CH:24]=3)([C:19]([F:22])([F:21])[F:20])[O:16][N:15]=2)=[CH:11][C:12]=1[CH3:13])=[O:7])C.Cl>C1COCC1.O>[Cl:30][C:25]1[CH:24]=[C:23]([C:17]2([C:19]([F:20])([F:22])[F:21])[O:16][N:15]=[C:14]([C:10]3[S:9][C:8]([C:6]([OH:7])=[O:5])=[C:12]([CH3:13])[CH:11]=3)[CH2:18]2)[CH:28]=[C:27]([Cl:29])[CH:26]=1

Participants

Conditions

Temperature: 50 °C

Procedure

LiOH (3.2 g) is added to a solution of 5-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-3-methyl-thiophene-2-carboxylic acid ethyl ester (9.88 g) in a mixture of THF and water (240 ml, 9:1). After 16 hours at room temperature, LiOH (1.05 g) and THF (150 ml) was added. The reaction mixture was heated at 50° C. for 10 hours. HCl (2N) was added to the reaction mixture until pH 1-2 was obtained. The mixture was then extracted three times with ethyl acetate. The organic phases were combined, washed with water and a saturated aqueous solution of NaCl, dried over Na2SO4 and concentrated in vacuo to yield 5-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-3-methyl-thiophene-2-carboxylic acid (9.3 g) as brown resin. The crude product is used without further purification.

Workup

customwas obtained
extractionThe mixture was then extracted three times with ethyl acetate
washwashed with water
dry with materiala saturated aqueous solution of NaCl, dried over Na2SO4
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-d30bf15524f84135b4c861a8c859bb4b
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08653116B2

Reaction notes

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