Dimethylformamide → tert-Butyl (2-chloro-3-formylpyridin-4-yl)carbamate

HRID 604983

Reaction equation

HRID 604983 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])[CH:5]=[CH:4][N:3]=1.C([Li])(C)(C)C.CCCCC.CN([CH:29]=[O:30])C>C1COCC1>[Cl:1][C:2]1[C:7]([CH:29]=[O:30])=[C:6]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:12])([CH3:14])[CH3:13])[CH:5]=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 21858447tert-butyl N-(2-chloropyridin-4-yl)carbamateHCID 178446069HCID 178446069, compound

Product 1

HCID 52987944tert-Butyl (2-chloro-3-formylpyridin-4-yl)carbamate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of tert-butyl (2-chloropyridin-4-yl)carbamate (1.14 gm, 5 mmol) in dry THF (20 mL) was cooled to −70° C. under an inert atmosphere and 1.7 M t-butyl lithium/pentane (8 mL, 13.5 mmol) was slowly added. The reaction was stirred for two hours and then dry DMF (1.2 mL, 15.5 mmol) was added. The reaction was allowed to slowly warm to room temperature over a three hour period. The reaction mixture was quenched with 3 N HCl (12 mL) and diluted with diethyl ether. The ether layer was washed with aqueous NaHCO3, dried (over Na2SO4), filtered and evaporated. The residue was triturated with cold diethyl ether to give pure t-butyl (2-chloro-3-formylpyridine-4-yl)carbamate. The mother liquors were chromatographed on silica gel eluting with 15-20% ethyl acetate/hexane to give additional product. 1H-NMR (500 MHz, CDCl3): δ 11.0 (1H, br s), 10.52 (1H, s), 8.38 (1H, d, J=6 Hz), 8.31 (1H, d, J=6 Hz), 1.54 (9H, s); m/e (m+1): 257.2.

Workup

  1. additionwas slowly added
  2. customThe reaction mixture was quenched with 3 N HCl (12 mL)
  3. additiondiluted with diethyl ether
  4. washThe ether layer was washed with aqueous NaHCO3
  5. dry with materialdried (over Na2SO4)
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was triturated with cold diethyl ether

Sources & evidence

ORD record
ord-6fd43be77bb74deda481ae6eb9976e73
Source dataset
uspto-grants-2011_03
Patent number
US07910561B2

Linked notes

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