5-Cyano-N-methoxy-N,2-dimethyl-6-oxo-4-p-tolyl-1,2,3,6-tetrahydropyridine-2-carboxamide → 6-Methyl-2-oxo-6-propioloyl-4-p-tolyl-1,2,5,6-tetrahydropyridine-3-carbonitrile

HRID 1629808Notes

Reaction equation

[C:1]([C:3]1[C:8](=[O:9])[NH:7][C:6]([CH3:16])([C:10](N(OC)C)=[O:11])[CH2:5][C:4]=1[C:17]1[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][CH:18]=1)#[N:2].[C:24]([Mg]Br)#[CH:25]>O1CCCC1>[CH3:16][C:6]1([C:10](=[O:11])[C:24]#[CH:25])[NH:7][C:8](=[O:9])[C:3]([C:1]#[N:2])=[C:4]([C:17]2[CH:18]=[CH:19][C:20]([CH3:23])=[CH:21][CH:22]=2)[CH2:5]1

Participants

Conditions

Temperature: 35 °C

Procedure

Intermediate 109A (0.0887 g, 0.283 mmol) was dissolved in tetrahydrofuran (1 mL) in a 25 mL 1 neck pear shaped flask that was equipped with a magnetic stirrer and an Ar inlet. Ethynylmagnesium bromide (5.66 mL, 2.83 mmol) was added dropwise and the reaction mixture was stirred at 35° C. for 4 h. The reaction mixture was cooled to rt, quenched with sat'd. aq NH4Cl (5 mL) and extracted with EtOAc (2×10 mL). The organic phases were combined and concentrated in vacuo. The residue was purified by silica gel chromatography (24 g silica gel, eluted with 0-100% EtOAc in hexanes) to give the desired product (0.06 g, 78%) as an orange solid. LCMS Anal. Calc'd for C12H14N2O2 278.1, found [M+H] 279.0.

Workup

customwas equipped with a magnetic stirrer
temperatureThe reaction mixture was cooled to rt
customquenched with sat'd
extractionaq NH4Cl (5 mL) and extracted with EtOAc (2×10 mL)
concentrationconcentrated in vacuo
customThe residue was purified by silica gel chromatography (24 g silica gel, eluted with 0-100% EtOAc in hexanes)

Sources & evidence

ORD record: ord-b387c49f064448898fdd3aa788346823
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08791091B2

Reaction notes

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