Diethyl Carbonate → Ethyl 2-(6-chloropyridin-2-yl)acetate

HRID 2235966Notes

Reaction equation

HRID 2235966 reaction equation
[Li]CCCC.[CH3:6][C:7]1[N:12]=[C:11]([Cl:13])[CH:10]=[CH:9][CH:8]=1.[C:14](=O)([O:18]CC)[O:15][CH2:16][CH3:17].[NH4+].[Cl-]>C1COCC1.O>[CH2:16]([O:15][C:14](=[O:18])[CH2:6][C:7]1[CH:8]=[CH:9][CH:10]=[C:11]([Cl:13])[N:12]=1)[CH3:17]

Participants

7

Reactant 4

HCID 7766Diethyl CarbonateHCID 25517Ammonium ChlorideHCID 876016-Chloro-2-picolineHCID 178418339Butyllithium

Product 1

HCID 18928624Ethyl 2-(6-chloropyridin-2-yl)acetateYield 60%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of n-BuLi (100 mL, 250 mmol of a 2.5 M solution in hexanes) in THF (200 mL) was added DIA (36 mL, 255 mmol) at 0° C. After stirring for 45 min, 6-methyl-2-chloropyridine (14.2 g, 111 mmol) was added slowly, maintaining the temperature <5° C. After 30 min, diethyl carbonate (30 mL, 250 mmol) was added dropwise maintaining the temperature below 10° C. The solution was stirred at 0° C. for 1 h, then water was slowly added, followed by the addition of a saturated solution of NH4Cl. The organic phase was dried (Na2SO4), filtered, and then concentrated under reduced pressure. The residue was purified through a pad of silica gel to give the product (13.3 g, 66.6 mmol) as a yellow oil. 1H NMR (400 MHz, CDCl3) δ 1.27 (t, 3H), 2.04 (s, 2H), 4.19 (q, 2H), 7.23 (dd, 2H), 7.62 (t, 1H).

Workup

  1. temperaturemaintaining the temperature <5° C
  2. waitAfter 30 min
  3. temperaturemaintaining the temperature below 10° C
  4. stirringThe solution was stirred at 0° C. for 1 h
  5. dry with materialThe organic phase was dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified through a pad of silica gel

Sources & evidence

ORD record
ord-3a41f1c23887446682037a3d2831267c
Source dataset
uspto-grants-2010_05
Patent number
US07714004B2

Reaction notes

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