Methyl iodide → 2-(3,5-Difluoro-4-methoxyphenyl)propanoic acid
Reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[F:11][C:12]1[CH:13]=[C:14]([CH2:21][C:22]([OH:24])=[O:23])[CH:15]=[C:16]([F:20])[C:17]=1[O:18][CH3:19].[CH3:25]I.[Cl-].[NH4+]>C1COCC1.O.C(OCC)(=O)C>[F:11][C:12]1[CH:13]=[C:14]([CH:21]([CH3:25])[C:22]([OH:24])=[O:23])[CH:15]=[C:16]([F:20])[C:17]=1[O:18][CH3:19]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 3
Conditions
- Temperature
- 0 °C
Procedure
Lithium bis(trimethylsilyl)amide (25.4 mL, 25.35 mmol) was added to 2-(3,5-difluoro-4-methoxyphenyl)acetic acid (2.5 g, 12.37 mmol) in THF (60.8 mL) cooled to 0° C. under nitrogen. The resulting solution was stirred at 0° C. for 30 minutes. Next Methyl iodide (0.925 mL, 14.84 mmol) was added and the reaction stirred for 30 minutes Ammonium chloride (satd) (50 mL) added with vigorous stirring, ethyl acetate (100 mL) and water (50 mL) were added and the organic phase separated, washed with water (50 mL) and saturated brine (50 mL). The aq layer was acidified with 2M HCl (50 mL) and extracted with ethyl acetate. The organic layers were combined and dried over MgSO4, filtered and evaporated to afford 2-(3,5-difluoro-4-methoxyphenyl)propanoic acid (2.81 g, 105%) which was used without further purification.
Workup
- additionwere added
- customthe organic phase separated
- washwashed with water (50 mL) and saturated brine (50 mL)
- extractionextracted with ethyl acetate
- dry with materialdried over MgSO4
- filtrationfiltered
- customevaporated
Sources & evidence
- ORD record
- ord-62892c92bbb945c5b38d69800f6c3067
- Source dataset
- uspto-grants-2012_05
- Patent number
- US08188092B2
Reaction notes
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