Methanol → 4-[5-(3,5-Dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-1-naphthalenecarboxylic acid

HRID 541083Notes

Reaction equation

HRID 541083 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([C:28]([F:31])([F:30])[F:29])[O:13][N:12]=[C:11]([C:14]3[C:23]4[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=4)[C:17]([C:24]([O:26]C)=[O:25])=[CH:16][CH:15]=3)[CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1.O.[OH-].[Li+].CO>O1CCCC1.O>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([C:28]([F:30])([F:29])[F:31])[O:13][N:12]=[C:11]([C:14]3[C:23]4[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=4)[C:17]([C:24]([OH:26])=[O:25])=[CH:16][CH:15]=3)[CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1

Participants

6

Reactant 3

HCID 887MethanolHCID 168937Lithium hydroxide, monohydrateHCID 58338637Methyl 4-[5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-1-naphthalenecarboxylate2×

Product 1

HCID 583386304-[5-(3,5-Dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-1-naphthalenecarboxylic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of methyl 4-[5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-1-naphthalenecarboxylate (i.e. the product from Step C) (650 mg, 1.39 mmol) in tetrahydrofuran (10 mL) was added a solution of lithium hydroxide monohydrate (350 mg, 8.34 mmol) in water (10 mL), followed by methanol (10 mL). The resulting mixture was stirred overnight at room temperature. The reaction mixture was partitioned between water and diethyl ether. Then the aqueous layer was acidified with 6 N aqueous hydrochloric acid to pH 2 and extracted with ethyl acetate. The combined organic layers were washed with brine, dried and concentrated to provide the title compound as a white solid (450 mg).

Workup

  1. customThe reaction mixture was partitioned between water and diethyl ether
  2. extractionextracted with ethyl acetate
  3. washThe combined organic layers were washed with brine
  4. customdried
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-9f2ae6c05436492daeb839fe9d397eb9
Source dataset
uspto-grants-2014_10
Patent number
US08871941B2

Reaction notes

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