alpha-Methylhydrocinnamic acid → 2-Butanone, 3-methyl-4-phenyl-

HRID 1366915Notes

Reaction equation

HRID 1366915 reaction equation
[CH3:1][Li].[CH3:3][CH:4]([CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[C:5]([OH:7])=O>CCOCC>[CH3:3][CH:4]([CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[C:5](=[O:7])[CH3:1]

Participants

4

Reactant 2

HCID 99862alpha-Methylhydrocinnamic acidHCID 178418348HCID 178418348, compound

Product 1

HCID 1028472-Butanone, 3-methyl-4-phenyl-

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

1.4 M Methyl lithium (34.8 mL, 48.72 mmol) was added over 70 min to a stirring 0° C. solution of α-methylhydrocinnamic acid (4.0019 g, 24.36 mmol) in dry Et2O (122 mL, 0.2 M): The ice bath was removed, and the reaction was allowed to stir at room temperature for 2 additional hours. The reaction was the poured into rapidly stirring ice water containing aq. HCl. The organic layer was removed, washed with NaHCO3 and brine, then dried with Na2SO4, filtered, concentrated, and purified by silica gel chromatography (Combiflash column, 95:5 Hexanes:EtOAc) to achieve pure 59 (2.3038 g, 58.3%): 1H (CDCl3, 400 MHz): δ 7.28 (2H, t, J=7.3 Hz), 7.20 (1H, t, J=7.3 Hz), 7.16 (2H, d, J=7.3 Hz), 3.00 (1H, dd, J=13.7, 6.8 Hz), 2.83 (1H, app sex, 7.0 Hz), 2.56 (1H, dd, J=13.7, 7.8 Hz), 2.08 (3H, s), 1.09 (3H, d, J=6.8 Hz) ppm. 13C (CDCl3, 100 MHz): δ 211.99, 139.53, 128.79, 128.28, 126.10, 48.65, 38.75, 28.74, 16.10 ppm. DEPT (CDCl3, 100 MHz): CH3 carbons: 28.74, 16.10; CH2 carbons: 38.75; CH carbons: 128.79, 128.28, 126.10, 48.65 ppm. HPLC: 10.229 min. (Note: SM has HPLC retention time of 9.225 min.)

Workup

  1. customThe ice bath was removed
  2. additionpoured into rapidly stirring ice water containing aq. HCl
  3. customThe organic layer was removed
  4. washwashed with NaHCO3 and brine
  5. dry with materialdried with Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. custompurified by silica gel chromatography (Combiflash column, 95:5 Hexanes:EtOAc)
  9. custom10.229 min. (Note: SM has HPLC retention time of 9.225 min.)

Sources & evidence

ORD record
ord-af9dbf13e76d43d386d607393b16569d
Source dataset
uspto-grants-2011_02
Patent number
US07893098B2

Reaction notes

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