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

HRID 1958869Notes

Reaction equation

HRID 1958869 reaction equation
O.[OH-].[Li+].[Cl:4][C:5]1[CH:6]=[C:7]([C:12]2([C:31]([F:34])([F:33])[F:32])[O:16][N:15]=[C:14]([C:17]3[C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[C:20]([C:27]([O:29]C)=[O:28])=[CH:19][CH:18]=3)[CH2:13]2)[CH:8]=[C:9]([Cl:11])[CH:10]=1.CO>O.O1CCCC1>[Cl:4][C:5]1[CH:6]=[C:7]([C:12]2([C:31]([F:33])([F:32])[F:34])[O:16][N:15]=[C:14]([C:17]3[C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[C:20]([C:27]([OH:29])=[O:28])=[CH:19][CH:18]=3)[CH2:13]2)[CH:8]=[C:9]([Cl:11])[CH:10]=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

A solution of lithium hydroxide monohydrate (350 mg, 8.34 mmol) in water (10 mL) was added to a stirred solution of methyl 4-[5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-1-naphthalenecarboxylate (i.e. the product of Step B, 650 mg, 1.39 mmol) in tetrahydrofuran (10 mL), followed by the addition of methanol (10 mL). The resulting mixture was stirred overnight at room temperature and then partitioned between water and diethyl ether. The aqueous layer was acidified with 6 N aqueous hydrochloric acid to pH 2 and extracted with ethyl acetate. The combined organic extracts were washed with brine, dried over sodium sulfate, and concentrated under reduced pressure to provide the title compound as a white solid (450 mg). 1H NMR (CDCl3): δ 9.08 (d, 1H), 8.80 (d, 1H), 8.31 (d, 1H), 7.71 (m, 2H), 7.57 (m, 3H), 7.46 (dd, 1H), 4.28 (d, 1H), 3.91 (d, 1H).

Workup

  1. custompartitioned between water and diethyl ether
  2. extractionextracted with ethyl acetate
  3. washThe combined organic extracts were washed with brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-102abcdeff0c4dfa8d949c24b6e2a2a4
Source dataset
uspto-grants-2013_04
Patent number
US08410153B2

Reaction notes

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