Methanol → 6-chloro-N,N-diethyl-4-o-tolyl-nicotinamide

HRID 379432Notes

Reaction equation

[C:1]1([CH3:9])[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[Mg]Cl.[Cl:10][C:11]1[CH:23]=[CH:22][C:14]([C:15]([N:17]([CH2:20][CH3:21])[CH2:18][CH3:19])=[O:16])=[CH:13][N:12]=1.CO.ClC1C(=O)C(C#N)=C(C#N)C(=O)C=1Cl>C1COCC1>[Cl:10][C:11]1[CH:23]=[C:22]([C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][C:1]=2[CH3:9])[C:14]([C:15]([N:17]([CH2:18][CH3:19])[CH2:20][CH3:21])=[O:16])=[CH:13][N:12]=1

Participants

Conditions

Temperature: 0 °C

Procedure

7.62 ml (7.62 mMol) o-Tolylmagnesium chloride solution (1M in THF) were added over 15 minutes to a solution of 0.60 g (2.54 mMol) 6-chloro-N,N-diethyl-nicotinamide in 3.0 ml THF cooled to 0° C. The reaction mixture was stirred 2 hours at room temperature, then cooled again to 0° C. and 0.41 ml methanol (10.1 mMol) were added followed by 692 mg 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (3.1 mMol). After stirring 2 hours at room temperature, the reaction mixture was concentrated under reduced pressure and 50 ml t-butyl-methylether were added at 50° C. The resulting suspension was filtered off, the filtrate was concentrated and the residue was purified by flash chromatography (eluent: ethyl acetate/n-heptane 1:1) to yield 0.67 g (86%) of 6-chloro-N,N-diethyl-4-o-tolyl-nicotinamide as a yellow oil.

Workup

temperaturecooled again to 0° C.
stirringAfter stirring 2 hours at room temperature
concentrationthe reaction mixture was concentrated under reduced pressure and 50 ml t-butyl-methylether
additionwere added at 50° C
filtrationThe resulting suspension was filtered off
concentrationthe filtrate was concentrated
customthe residue was purified by flash chromatography (eluent: ethyl acetate/n-heptane 1:1)

Sources & evidence

ORD record: ord-48fab08712d94deebfc8aa9ab8fe1b9f
Source dataset: uspto-grants-2001_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06297375B1

Reaction notes

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