Dimethylformamide → N-(5-formyl-pyridin-2-yl)-2,2-dimethyl-propionamide

HRID 1454835Notes

Reaction equation

Br[C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9](=[O:14])[C:10]([CH3:13])([CH3:12])[CH3:11])=[N:6][CH:7]=1.C([Li])CCC.CN(C)[CH:22]=[O:23].COC(C)(C)C>C1COCC1>[CH:22]([C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9](=[O:14])[C:10]([CH3:13])([CH3:12])[CH3:11])=[N:6][CH:7]=1)=[O:23]

Participants

Conditions

Temperature: -70 °C

Procedure

A solution of N-(5-Bromo-pyridin-2-yl)-2,2-dimethyl-propionamide (8.7 g, Kelly, Tetrahedron Lett., 32, 1991, 4263) in THF (200 mL) was cooled to −70° C. under an argon atmosphere and treated dropwise over 30 minutes with n-butyllithium (45.78 mL, 1.6 M in hexane, Acros). The mixture was stirred 1 h at −70° C. and then treated dropwise (over 10 minutes, at −70° C.) with a mixture of N,N-dimethylformamide (5.25 mL) in THF (5 mL), and stirring was continued for further 30 minutes. The reaction mixture was then poured into 2M aqueous KHCO3 (1.2 L), tert-butyl methyl ether (1.2 L) was added, and after stirring for 20 minutes, the layers were separated, the organic layer extracted twice with tert-butyl methyl ether (total volume 0.3 L). The combined organic layers were dried over sodium sulphate, filtered and evaporated in vacuo to give N-(5-formyl-pyridin-2-yl)-2,2-dimethyl-propionamide (7 g) as an yellow oil that was used directly in the next step.

Workup

additiontreated dropwise (over 10 minutes, at −70° C.)
stirringstirring
waitwas continued for further 30 minutes
additionwas added
stirringafter stirring for 20 minutes
customthe layers were separated
extractionthe organic layer extracted twice with tert-butyl methyl ether (total volume 0.3 L)
dry with materialThe combined organic layers were dried over sodium sulphate
filtrationfiltered
customevaporated in vacuo

Sources & evidence

ORD record: ord-6eeadfc4068749f28cf57ba531f93cae
Source dataset: uspto-grants-2009_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07482341B2

Reaction notes

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