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

HRID 2167007Notes

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-5cc6d25c4ea14db9a365705d5ac61f2a
Source dataset: uspto-grants-2015_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09044389B2

Reaction notes

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