Methyl iodide → Methyl 4-fluoro-alpha-methylbenzeneacetate

HRID 1051865Notes

Reaction equation

HRID 1051865 reaction equation
[CH:1](NC(C)C)(C)C.C([Li])CCC.[F:13][C:14]1[CH:19]=[CH:18][C:17]([CH2:20][C:21]([O:23][CH3:24])=[O:22])=[CH:16][CH:15]=1.CI>O1CCCC1.CCCCCC.O>[F:13][C:14]1[CH:15]=[CH:16][C:17]([CH:20]([CH3:1])[C:21]([O:23][CH3:24])=[O:22])=[CH:18][CH:19]=1

Participants

8

Reactant 4

HCID 6328Methyl iodideHCID 7912DiisopropylamineHCID 2733233Methyl 2-(4-fluorophenyl)acetateHCID 178418339Butyllithium

Product 1

HCID 11389760Methyl 4-fluoro-alpha-methylbenzeneacetateYield 96.9%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of diisopropylamine (13.0 g) in tetrahydrofurane (160 mL) was added a solution of n-butyllithium in hexane (51.4 mL; c=2.5 M) at −78° C. The solution was stirred at 0° C. for 15 minutes. The solution was cooled to −78° C. and a solution of methyl (4-fluorophenyl)acetate (18.0 g), dissolved in tetrahydrofurane (40 mL) was added. The solution was stirred at −78° C. for 30 minutes. Methyl iodide (10.0 mL) was added at −78° C., and the solution was allowed to warm up to 0° C. within 1 h. Water was added and the reaction mixture was extracted with ethyl acetate. The organic phase was dried (sodium sulfate) and the solvent was removed in vacuum. Silicagel chromatography gave 18.9 g of the title compound.

Workup

  1. temperatureThe solution was cooled to −78° C.
  2. additionwas added
  3. stirringThe solution was stirred at −78° C. for 30 minutes
  4. temperatureto warm up to 0° C. within 1 h
  5. extractionthe reaction mixture was extracted with ethyl acetate
  6. dry with materialThe organic phase was dried (sodium sulfate)
  7. customthe solvent was removed in vacuum

Sources & evidence

ORD record
ord-e2ac11216b984749951074ec26cb127c
Source dataset
uspto-grants-2016_07
Patent number
US09388177B2

Reaction notes

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