Hydrochloric Acid → 2-methyl-6-phenyl-1H-pyridin-4-one

HRID 418045Notes

Reaction equation

C[C:2]1([CH3:10])[CH2:7][CH2:6][CH2:5][C:4]([CH3:9])(C)[NH:3]1.[Li][CH2:12][CH2:13][CH2:14][CH3:15].Cl.[OH-:17].[Na+].[CH2:19]1COCC1>C(#N)C1C=CC=CC=1>[CH3:9][C:4]1[NH:3][C:2]([C:10]2[CH:19]=[CH:12][CH:13]=[CH:14][CH:15]=2)=[CH:7][C:6](=[O:17])[CH:5]=1

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of 2,2,6,6-tetramethylpiperidine (18.2 ml) in THF (160 ml) at −78° C. was added dropwise n-BuLi (43 ml, 2.5M solution in Hex). After the addition, the reaction mixture was stirred for 30 min at −78° C. To this solution was added intermediate 1.1 (6.17 g) in THF (20 ml) at −78° C. After addition, stirring was continued for 30 min. A solution of benzonitrile (4.67 ml) in THF (20 ml) at −78° C. was added dropwise. After addition, the mixture was slowly warmed to −50° C. and stirred for 20 min. The solution was poured into 10% aq. HCl (200 ml), stirred for 45 min at RT and neutralized with aq. NaOH to pH 9-10. The org. phase was separated, the aq. phase extracted twice with EA, and the combined org. phases dried over MgSO4. CC (Hept/EA 1:1, then DCM/MeOH 95:5, then DCM/MeOH 8:2) afforded 1.96 g of the desired compound.

Workup

additionAfter the addition
additionAfter addition
stirringstirring
waitwas continued for 30 min
additionAfter addition
temperaturethe mixture was slowly warmed to −50° C.
stirringstirred for 20 min
customphase was separated
extractionthe aq. phase extracted twice with EA
dry with materialphases dried over MgSO4

Sources & evidence

ORD record: ord-2917b1119c02460c998dcc5b7d2fd99b
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08093250B2

Reaction notes

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