Benzonitrile → 2-methyl-6-phenyl-1H-pyridin-4-one
Reaction equation
C[C:2]1([CH3:10])[CH2:7][CH2:6][CH2:5][C:4]([CH3:9])(C)[NH:3]1.C([Li])CCC.[C:16](#N)[C:17]1C=C[CH:20]=[CH:19][CH:18]=1.C1C[O:27]CC1>>[CH3:9][C:4]1[NH:3][C:2]([C:10]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:7][C:6](=[O:27])[CH:5]=1Participants
Conditions
- Temperature
- -56 °C
Procedure
To a −78° C. cooled solution of 2,2,6,6-tetramethylpiperidine (157 g) in THF (830 mL) was added n-butyllithium (1.6 M in hexane, 697 mL) over 45 min. After 25 min stirring at −78° C. a solution of intermediate 1.4 (63 g) in THF (200 mL) was added to the mixture over 25 min, followed by a solution of benzonitrile (47.9 mL) in THF (200 mL) over 30 min. The cooling bath was removed and the mixture was allowed to warm to −56° C. over 1.5 h. HCl (32%, 186.5 g) was added, followed by water (400 mL) and THF (200 mL). The phases were separated. The org. phase was washed with water and HCl (32%, 150 mL) was added, followed by water (200 mL). The phases were separated and the aq. phase was evaporated off. The residue was taken up in toluene and evaporated to dryness to afford 249 g of the desired compound with 13% purity. No further purification was performed.
Workup
- additionwas added to the mixture over 25 min
- customThe cooling bath was removed
- additionHCl (32%, 186.5 g) was added
- customThe phases were separated
- washphase was washed with water and HCl (32%, 150 mL)
- additionwas added
- customThe phases were separated
- customthe aq. phase was evaporated off
- customevaporated to dryness
Sources & evidence
- ORD record
- ord-0aac7dbfa6144fb6b500895bb8f582e8
- Source dataset
- uspto-grants-2011_11
- Patent number
- US08058263B2
Reaction notes
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