Hydrochloric Acid → 4-(4-Ethyl-5-fluoro-2-methoxyphenoxy)-3-fluorobenzoic acid
Reaction equation
[CH2:1]([C:3]1[C:18]([F:19])=[CH:17][C:6]([O:7][C:8]2[CH:15]=[CH:14][C:11]([C:12]#N)=[CH:10][C:9]=2[F:16])=[C:5]([O:20][CH3:21])[CH:4]=1)[CH3:2].[OH-:22].[Na+].Cl.C[OH:26]>C(OCC)(=O)C.O>[CH2:1]([C:3]1[C:18]([F:19])=[CH:17][C:6]([O:7][C:8]2[CH:15]=[CH:14][C:11]([C:12]([OH:26])=[O:22])=[CH:10][C:9]=2[F:16])=[C:5]([O:20][CH3:21])[CH:4]=1)[CH3:2]Participants
7
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 70 °C
Procedure
To a solution of 4-(4-ethyl-5-fluoro-2-methoxyphenoxy)-3-fluorobenzonitrile (420 mg, 1.45 mmol; which may be prepared as described in D1) in methanol (15 mL) was added an aqueous solution of 6N NaOH (7.3 mL, 43.6 mmol). The reaction mixture was heated to reflux (70° C.) and stirred overnight. After cooling with an ice bath, concentrated HCl (3.7 mL) was added slowly. The mixture was diluted with ethyl acetate and water. The aqueous layer was separated and extracted twice with ethyl acetate. The combined organic phases were dried over sodium sulfate, filtrated and concentrated in vacuo to give the title product as a beige solid (447 mg, quantitative).
Workup
- temperatureThe reaction mixture was heated
- temperatureAfter cooling with an ice bath
- customThe aqueous layer was separated
- extractionextracted twice with ethyl acetate
- dry with materialThe combined organic phases were dried over sodium sulfate
- filtrationfiltrated
- concentrationconcentrated in vacuo
Sources & evidence
- ORD record
- ord-1491165ada964fb89cff1c0a6f394885
- Source dataset
- uspto-grants-2014_01
- Patent number
- US08623865B2
Reaction notes
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