Triethylamine → Methyl 6-methoxy-5-methylpyridine-3-carboxylate

HRID 1432876Notes

Reaction equation

HRID 1432876 reaction equation
I[C:2]1[CH:3]=[C:4]([CH3:10])[C:5]([O:8][CH3:9])=[N:6][CH:7]=1.CCN(CC)CC.CN([CH:21]=[O:22])C.[CH3:23][OH:24]>>[CH3:23][O:24][C:21](=[O:22])[C:2]1[CH:3]=[C:4]([CH3:10])[C:5]([O:8][CH3:9])=[N:6][CH:7]=1

Participants

4

Reactant 3

HCID 8471TriethylamineHCID 21901440N,N-dimethylformamide methanolHCID 534159905-Iodo-2-methoxy-3-methylpyridine

Product 1

HCID 54292198Methyl 6-methoxy-5-methylpyridine-3-carboxylateYield 57%

Conditions

Temperature
0 °C

Procedure

A solution containing 5-iodo-3-methyl-2-methoxy-pyridine (10.0 g, 40.0 mmol), Et3N (8.0 g, 80.0 mmol), and (Ph3P)4PdCl2 (2.80 g, 4.00 mmol) in 1:1 DMF/MeOH (100 mL) is cooled to 0° C. Carbon monoxide is bubbled into the cooled solution for approx. 5 min at which time the reaction mixture is sealed under a balloon of CO. The reaction mixture is allowed to warm to ambient temperature and then stirred for 16 hours. The reaction mixture is concentrated in vacuo and the residue is partitioned between water (300 mL) and EtOAc (300 mL) and the layers are separated. The organic phase is washed with brine, dried over anhydrous Na2SO4, filtered and concentrated. The crude product is purified by silica gel flash column chromatography (hexane/diethyl ether, 19:1) to provide 4.10 g (57%) of the title compound as a white solid. 1H NMR (300 MHz, CDCl3) δ2.20 (s, 3H), 3.88 (s, 3H), 4.00 (s, 2H), 7.96 (d, J=2.2 Hz, 1H), 8.65 (d, J=2.2 Hz, 1H) ppm; MS (ISP loop): m/z 182 (M+H).

Workup

  1. customCarbon monoxide is bubbled into the cooled solution for approx. 5 min at which time the reaction mixture
  2. customis sealed under a balloon of CO
  3. temperatureto warm to ambient temperature
  4. concentrationThe reaction mixture is concentrated in vacuo
  5. customthe residue is partitioned between water (300 mL) and EtOAc (300 mL)
  6. customthe layers are separated
  7. washThe organic phase is washed with brine
  8. dry with materialdried over anhydrous Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe crude product is purified by silica gel flash column chromatography (hexane/diethyl ether, 19:1)

Sources & evidence

ORD record
ord-bfa0f197d11e46c9865c7a10f08250dc
Source dataset
uspto-grants-2009_11
Patent number
US07612075B2

Reaction notes

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