N-Methyl-N-(pyridine-2-yl)formamide → 5-(Benzyloxy)-3-bromo-1-methyl-6-oxo-1,6-dihydropyridine-2-carbaldehyde

HRID 625969Notes

Reaction equation

[CH2:1]([O:8][C:9]1[C:10](=[O:18])[N:11]([CH3:17])[C:12](Br)=[C:13]([Br:15])[CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([Mg]Cl)(C)C.CN(C1C=CC=CN=1)[CH:26]=[O:27]>C1COCC1>[CH2:1]([O:8][C:9]1[C:10](=[O:18])[N:11]([CH3:17])[C:12]([CH:26]=[O:27])=[C:13]([Br:15])[CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

Conditions

Temperature: -78 °C

Procedure

To a −78° C. solution of 3-(benzyloxy)-5,6-dibromo-1-methylpyridin-2(1H)-one (1.5 g, 4.02 mmol) in THF (20 mL) was added 2 M isopropylmagnesium chloride in THF (4.02 mL, 8.04 mmol) dropwise. This mixture was stirred at −78° C. for 15 minutes under nitrogen, and N-methyl-N-pyridin-2-ylformamide (1.4 mL, 12.06 mmol) was added. The mixture was allowed to slowly warm to room temperature overnight. Volatiles were removed under reduced pressure, and the resulting residue was partitioned between dilute aqueous hydrochloric acid and ethyl acetate. The aqueous layer was removed and discarded. The organic layer was collected, dried over anhydrous magnesium sulfate, and purified by silica gel chromatography to afford 5-(benzyloxy)-3-bromo-1-methyl-6-oxo-1,6-dihydropyridine-2-carbaldehyde (1.09 g, 3.38 mmol, 84% yield). ES-MS (M+H)+=323.

Workup

temperatureto slowly warm to room temperature overnight
customVolatiles were removed under reduced pressure
customthe resulting residue was partitioned between dilute aqueous hydrochloric acid and ethyl acetate
customThe aqueous layer was removed
customThe organic layer was collected
dry with materialdried over anhydrous magnesium sulfate
custompurified by silica gel chromatography

Sources & evidence

ORD record: ord-975b92a1dad04d289fe25a2fe9fad3de
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09309199B2

Reaction notes

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