Hydrochloric Acid → 1-[2-(2-bromo-4,5-dimethoxy-phenyl)-acetyl]-2-phenyl-2,3-dihydro-1H-pyridin-4-one
Reaction equation
C[O:2][C:3]1[CH:8]=[CH:7][N:6]=[CH:5][CH:4]=1.[C:9]1([Mg]Br)[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.[Br:17][C:18]1[CH:23]=[C:22]([O:24][CH3:25])[C:21]([O:26][CH3:27])=[CH:20][C:19]=1[CH2:28][C:29](Cl)=[O:30].Cl>C1COCC1>[Br:17][C:18]1[CH:23]=[C:22]([O:24][CH3:25])[C:21]([O:26][CH3:27])=[CH:20][C:19]=1[CH2:28][C:29]([N:6]1[CH:7]=[CH:8][C:3](=[O:2])[CH2:4][CH:5]1[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)=[O:30]Participants
Conditions
- Temperature
- -25 °C
Procedure
To a stirring solution of 4-methoxypyridine (336 mg, 3.08 mmol) in THF (7 mL) at −25° C. was added phenylmagnesium bromide (3M in ether, 1.13 mL, 3.39 mmol) under Ar atmosphere. After 5 minutes a solution of (2-bromo-4,5-dimethoxy-phenyl)-acetyl chloride (904 mg, 3.08 mL) in THF (2 mL) was added slowly. The mixture was stirred at −25° C. for 90 minutes. 2N HCl was added at −25° C., and the mixture was allowed to warm to room temperature and was stirred for 10 minutes. The mixture was extracted with ethyl acetate, and the combined organic extracts were washed with brine, dried (Na2SO4), filtered and concentrated to dryness under reduced pressure. Purification of the residue by flash chromatography (hexane/ethyl acetate gradient) gave 1-[2-(2-bromo-4,5-dimethoxy-phenyl)-acetyl]-2-phenyl-2,3-dihydro-1H-pyridin-4-one (742 mg, 57%). MS (M+H) 431.
Workup
- temperatureto warm to room temperature
- stirringwas stirred for 10 minutes
- extractionThe mixture was extracted with ethyl acetate
- washthe combined organic extracts were washed with brine
- dry with materialdried (Na2SO4)
- filtrationfiltered
- concentrationconcentrated to dryness under reduced pressure
- customPurification of the residue by flash chromatography (hexane/ethyl acetate gradient)
Sources & evidence
- ORD record
- ord-3d523065cdf143708c5c54a80afa6892
- Source dataset
- uspto-grants-2012_04
- Patent number
- US08153808B2
Reaction notes
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