Ethyl 3-chloro-3-oxopropionate → Ethyl 3-[(3-ethoxy-3-oxopropanoyl)amino]-5-(4-fluorobenzyl)pyridine-2-carboxylate

HRID 2364129Notes

Reaction equation

HRID 2364129 reaction equation
Cl[C:2](=[O:9])[CH2:3][C:4]([O:6][CH2:7][CH3:8])=[O:5].[NH2:10][C:11]1[C:12]([C:25]([O:27][CH2:28][CH3:29])=[O:26])=[N:13][CH:14]=[C:15]([CH2:17][C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=2)[CH:16]=1>ClCCCl>[CH2:7]([O:6][C:4](=[O:5])[CH2:3][C:2]([NH:10][C:11]1[C:12]([C:25]([O:27][CH2:28][CH3:29])=[O:26])=[N:13][CH:14]=[C:15]([CH2:17][C:18]2[CH:19]=[CH:20][C:21]([F:24])=[CH:22][CH:23]=2)[CH:16]=1)=[O:9])[CH3:8]

Participants

4

Reactant 2

HCID 118931Ethyl 3-chloro-3-oxopropionateHCID 42637772Ethyl 3-amino-5-(4-fluorobenzyl)picolinate

Product 1

HCID 42637836Ethyl 3-[(3-ethoxy-3-oxopropanoyl)amino]-5-(4-fluorobenzyl)pyridine-2-carboxylate

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

Ethyl 3-chloro-3-oxopropionate (1.32 g, 8.75 mmol) was added to a solution of ethyl 3-amino-5-(4-fluorobenzyl)-2-pyridinecarboxylate (2 g, 7.29 mmol) in DCE (20 mL) and the solution was heated at reflux for 1 h. The solvent was removed in vacuo and silica gel chromatography eluting with 0-5% MeOH/CH2Cl2 provide the product as an amber oil: 1H NMR (CDCl3) δ 8.96 (1H, br s), 8.32 (1H, d, J=1.8 Hz), 7.17 (2H, dd, J˜9, 6 Hz), 7.00 (2H, t, J˜9 Hz), 4.53 (2H, t, J=7 Hz), 4.29 (2H, t, J=7 Hz), 4.02 (2H, s), 3.54 (2H, s), 1.48 (3H, t, J=7 Hz), 1.33 (3H, t, J=7 Hz).

Workup

  1. temperaturethe solution was heated
  2. temperatureat reflux for 1 h
  3. customThe solvent was removed in vacuo and silica gel chromatography
  4. washeluting with 0-5% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-1d233f71c3b94b649007f4e930b144b9
Source dataset
uspto-grants-2014_04
Patent number
US08691991B2

Reaction notes

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