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

HRID 2364212Notes

Reaction equation

HRID 2364212 reaction equation
[F:1][C:2]1[CH:27]=[CH:26][C:5]([CH2:6][C:7]2[CH:8]=[C:9]([NH:18][C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=3)[C:10]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[N:11][CH:12]=2)=[CH:4][CH:3]=1.Cl[C:29](=[O:36])[CH2:30][C:31]([O:33][CH2:34][CH3:35])=[O:32].CO.ClCCl>ClCCCl>[CH2:34]([O:33][C:31](=[O:32])[CH2:30][C:29]([N:18]([C:19]1[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=1)[C:9]1[C:10]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[N:11][CH:12]=[C:7]([CH2:6][C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:27][CH:26]=2)[CH:8]=1)=[O:36])[CH3:35]

Participants

5

Reactant 3

HCID 118931Ethyl 3-chloro-3-oxopropionateHCID 21226129Dichloromethane methanolHCID 69482193Ethyl 5-(4-fluorobenzyl)-3-[(4-fluorophenyl)amino]pyridine-2-carboxylate

Product 1

HCID 69481480Ethyl 3-[(3-ethoxy-3-oxopropanoyl)(4-fluorophenyl)amino]-5-(4-fluorobenzyl)pyridine-2-carboxylateYield 80%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a solution of ethyl 5-(4-fluorobenzyl)-3-[(4-fluorophenyl)amino]pyridine-2-carboxylate (456 mg, 1.24 mmol) in 1,2-dichloroethane was added ethyl 3-chloro-3-oxopropanoate (0.18 mL, 2.36 mmol) and the resulting yellow solution was refluxed for 1 hour or until determined complete by TLC (5% methanol/dichloromethane). The mixture was cooled to ambient temperature, quenched with water and extracted with dichloromethane. The organics were washed with saturated aqueous sodium bicarbonate, brine, and dried over sodium sulfate to yield ethyl 3-[[3-(ethyloxy)-3-oxopropanoyl](4-fluorophenyl)amino]-5-[(4-fluorophenyl)methyl]-2-pyridinecarboxylate (477 mg, 80% yield) as mixture of rotamers. The yellow oil can be carried on without further purification or purified by silica gel chromatography (0-12% methanol/dichloromethane gradient elution). Spectral data was consistent with the expected product as mixture of rotamers. MS m/z 505 (M+23).

Workup

  1. temperaturethe resulting yellow solution was refluxed for 1 hour
  2. customquenched with water
  3. extractionextracted with dichloromethane
  4. washThe organics were washed with saturated aqueous sodium bicarbonate, brine
  5. dry with materialdried over sodium sulfate

Sources & evidence

ORD record
ord-0aee52c5584a4fac922b3221e8569882
Source dataset
uspto-grants-2014_04
Patent number
US08691991B2

Reaction notes

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