Dimethylformamide → N-(5-Fluoro-3-formylpyridin-2-yl)-2,2-dimethylpropanamide

HRID 1255397Notes

Reaction equation

HRID 1255397 reaction equation
[F:1][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]>C(OCC)C>[F:1][C:2]1[CH:3]=[C:4]([CH:22]=[O:23])[C:5]([NH:8][C:9](=[O:14])[C:10]([CH3:11])([CH3:13])[CH3:12])=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 22293237N-(5-Fluoropyridin-2-yl)pivalamideHCID 178418339Butyllithium

Product 1

HCID 46318086N-(5-Fluoro-3-formylpyridin-2-yl)-2,2-dimethylpropanamide

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
-78 °C

Procedure

To a stirred solution of N-(5-fluoro-pyridin-2-yl)-2,2-dimethylpropionamide (39.2 g) in dry diethyl ether (1200 ml) under an atmosphere of nitrogen at −78° C. was added dropwise t.-butyl lithium in hexanes (1.7M, 300 ml). The mixture was stirred at −78° C. for 2 hours then dry N,N-dimethylformamide (160 ml) was added and the slurry stirred at −78° C. for 1 hour then allowed to slowly warm to ambient temperature and stirred for an additional 1 hour. The mixture was quenched with aqueous 2M hydrochloric acid until a clear biphasic solution was formed and the organic phase separated. The aqueous phase was further extracted with diethyl ether. The extracts were combined, washed with brine (300 ml), dried over magnesium sulfate, filtered and evaporated under reduced pressure to give the required product as a pale yellow solid, 40 g. 1H NMR (CDCl3) δ: 11.20 (1H, s), 9.94 (1H, s), 8.59 (1H, d), 7.84 (1H, dd), 1.42 (9H, s).

Workup

  1. stirringthe slurry stirred at −78° C. for 1 hour
  2. temperatureto slowly warm to ambient temperature
  3. stirringstirred for an additional 1 hour
  4. customThe mixture was quenched with aqueous 2M hydrochloric acid until a clear biphasic solution
  5. customwas formed
  6. customthe organic phase separated
  7. extractionThe aqueous phase was further extracted with diethyl ether
  8. washwashed with brine (300 ml)
  9. dry with materialdried over magnesium sulfate
  10. filtrationfiltered
  11. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-550dc14b6f53483e8478c31d4975628c
Source dataset
uspto-grants-2013_06
Patent number
US08461083B2

Reaction notes

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