Ethyl Bromide → 4-(2,5-Difluorobenzoyl)-1-methylpiperidine
Reaction equation
BrCC.Cl[CH:5]1[CH2:10][CH2:9][N:8]([CH3:11])[CH2:7][CH2:6]1.N1CCCCC1.[F:18][C:19]1[CH:26]=[CH:25][C:24]([F:27])=[CH:23][C:20]=1[C:21]#N.[NH4+].[Cl-].[OH2:30]>O1CCCC1>[F:18][C:19]1[CH:26]=[CH:25][C:24]([F:27])=[CH:23][C:20]=1[C:21]([CH:5]1[CH2:10][CH2:9][N:8]([CH3:11])[CH2:7][CH2:6]1)=[O:30]Participants
Reactant 5
Product 1
Reagents, catalysts & solvents 1
Procedure
To a stirred suspension of Mg (9.62 g, 0.40 moles) in tetrahydrofuran (THF) (45 ml) was added a few ml of bromoethane to initiate the reaction followed by dropwise addition of freshly distilled 4-chloro-N-methylpiperidine (42.3 g, 6.32 moles) in THF (140 ml). The reaction was initiated with a high intensity heat gun and controlled by the rate of addition of the piperidine. After the addition was complete, the reaction was refluxed for 1 hour. Next 2,5-difluorobenzonitrile (48.2 g, 0.318 moles) in THF (20 ml) was added and the reaction was refluxed for an additional 3 hours. The reaction was allowed to stand for 65 hours and was then poured into a solution of NH4Cl/H2O (120 g/400 ml). The mixture was heated on a steam bath for 2 hours, cooled and extracted with ether (500 ml.). Concentration produced an oil (50.6 g) which the product was distilled from (112° [email protected] mm) to yield 30.4 g (40%) of the product.
Workup
- temperatureheat gun
- additionAfter the addition
- temperaturethe reaction was refluxed for 1 hour
- temperaturethe reaction was refluxed for an additional 3 hours
- temperatureThe mixture was heated on a steam bath for 2 hours
- temperaturecooled
- extractionextracted with ether (500 ml.)
- concentrationConcentration
Sources & evidence
- ORD record
- ord-c0ae5e12e6f44a668aac1b6aeb9051b3
- Source dataset
- uspto-grants-1989_08
- Patent number
- US04853470
Reaction notes
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