Methyl iodide → Ethyl 2-(2-chloropyridin-4-yl)propanoate

HRID 2069057Notes

Reaction equation

HRID 2069057 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH:5]=[CH:4][N:3]=1.[CH3:14][Si]([N-][Si](C)(C)C)(C)C.[K+].CI.[NH4+].[Cl-]>C1COCC1.CCOCC>[Cl:1][C:2]1[CH:7]=[C:6]([CH:8]([CH3:14])[C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH:5]=[CH:4][N:3]=1

Participants

7

Reactant 4

HCID 6328Methyl iodideHCID 25517Ammonium ChlorideHCID 3251421Potassium bis(trimethylsilyl)amideHCID 57709236Ethyl 2-(2-chloropyridin-4-yl)acetate

Product 1

HCID 58532560Ethyl 2-(2-chloropyridin-4-yl)propanoateYield 58.7%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of ethyl 2-(2-chloropyridin-4-yl)acetate (44) (2.5 g, 12.52 mmol) in THF (25 mL), under nitrogen at −78° C. was added a solution of KHMDS (0.5M in toluene, 26.3 mL, 13.2 mmol). The mixture was warmed to RT for 10 min, then re-cooled to −78° C. and methyl iodide (0.820 mL, 13.15 mmol) added in a single portion and the mixture allowed to warm to RT. Saturated aqueous NH4Cl solution was added and the mixture was diluted with ether. The organic layer was washed with water and brine and then dried (MgSO4) and evaporated in vacuo. The residue was purified by flash column chromatography (SiO2, 100 g, 5-10% EtOAc in isohexane, gradient elution) to afford the title compound (51) (1.57 g, 56%): m/z 214 (M+H)+ (ES+).

Workup

  1. temperaturere-cooled to −78° C.
  2. temperatureto warm to RT
  3. washThe organic layer was washed with water and brine
  4. dry with materialdried (MgSO4)
  5. customevaporated in vacuo
  6. customThe residue was purified by flash column chromatography (SiO2, 100 g, 5-10% EtOAc in isohexane, gradient elution)

Sources & evidence

ORD record
ord-317a700bc2cb439fab0e4f357e09ab54
Source dataset
uspto-grants-2012_10
Patent number
US08299073B2

Reaction notes

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