Diethyl Carbonate → Ethyl 2-(3-methoxypyridin-2-yl)acetate

HRID 523255Notes

Reaction equation

HRID 523255 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[CH3:13][O:14][C:15]1[C:16]([CH3:21])=[N:17][CH:18]=[CH:19][CH:20]=1.[C:22](=O)([O:26]CC)[O:23][CH2:24][CH3:25]>C1COCC1>[CH3:13][O:14][C:15]1[C:16]([CH2:21][C:22]([O:23][CH2:24][CH3:25])=[O:26])=[N:17][CH:18]=[CH:19][CH:20]=1

Participants

6

Reactant 4

HCID 7766Diethyl CarbonateHCID 7912DiisopropylamineHCID 30152703-Methoxy-2-methylpyridineHCID 178418339Butyllithium

Product 1

HCID 59636754Ethyl 2-(3-methoxypyridin-2-yl)acetateYield 81%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A stirred solution of diisopropylamine (0.385 mL, 2.70 mmol) in THF (2 mL) at 0° C. was treated slowly with 1.6 M n-butyllithium in hexanes (1.69 mL, 2.70 mmol). The mixture was stirred for 15 min, then was added over 5 min to a stirred solution of 3-methoxy-2-picoline (0.133 g, 1.08 mmol) and diethyl carbonate (0.262 mL, 2.16 mmol) in THF (5 mL) at −78° C. After stirring for 45 min more, the cooling bath was removed and stirring was continued overnight at room temperature. The mixture was treated with saturated aqueous NH4Cl and diluted with EtOAc. The organic phase was separated, washed sequentially with saturated aqueous NaHCO3 and brine, and dried and concentrated. The residue was purified by column chromatography on silica gel (12 g), eluting with 50% EtOAc-hexanes, to provide ethyl 2-(3-methoxypyridin-2-yl)acetate as an oil (0.17 g, 81% yield). Mass spectrum m/z 196 (M+H)+.

Workup

  1. stirringAfter stirring for 45 min more
  2. customthe cooling bath was removed
  3. stirringstirring
  4. waitwas continued overnight at room temperature
  5. additionThe mixture was treated with saturated aqueous NH4Cl
  6. additiondiluted with EtOAc
  7. customThe organic phase was separated
  8. washwashed sequentially with saturated aqueous NaHCO3 and brine
  9. customdried
  10. concentrationconcentrated
  11. customThe residue was purified by column chromatography on silica gel (12 g)
  12. washeluting with 50% EtOAc-hexanes

Sources & evidence

ORD record
ord-fb509d29027e43b1975bb41b289378e2
Source dataset
uspto-grants-2016_05
Patent number
US09334290B2

Reaction notes

Loading…