Ethyl 3-chloro-3-oxopropionate → Methyl 3-{cyclopropyl[3-(ethyloxy)-3-oxopropanoyl]amino}-5-[(4-fluorophenyl)methyl]-2-pyridinecarboxylate

HRID 2364529Notes

Reaction equation

HRID 2364529 reaction equation
[CH:1]1([NH:4][C:5]2[C:6]([C:19]([O:21][CH3:22])=[O:20])=[N:7][CH:8]=[C:9]([CH2:11][C:12]3[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=3)[CH:10]=2)[CH2:3][CH2:2]1.Cl[C:24](=[O:31])[CH2:25][C:26]([O:28][CH2:29][CH3:30])=[O:27].C(=O)(O)[O-].[Na+]>ClCCl>[CH:1]1([N:4]([C:24](=[O:31])[CH2:25][C:26]([O:28][CH2:29][CH3:30])=[O:27])[C:5]2[C:6]([C:19]([O:21][CH3:22])=[O:20])=[N:7][CH:8]=[C:9]([CH2:11][C:12]3[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=3)[CH:10]=2)[CH2:2][CH2:3]1

Participants

5

Reactant 3

HCID 118931Ethyl 3-chloro-3-oxopropionateHCID 516892Sodium BicarbonateHCID 69481047Methyl 3-(cyclopropylamino)-5-[(4-fluorophenyl)methyl]-2-pyridinecarboxylate

Product 1

HCID 69480475Methyl 3-{cyclopropyl[3-(ethyloxy)-3-oxopropanoyl]amino}-5-[(4-fluorophenyl)methyl]-2-pyridinecarboxylateYield 88.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of methyl 3-(cyclopropylamino)-5-[(4-fluorophenyl)methyl]-2-pyridinecarboxylate (234 mg, 0.78 mmol) and ethyl 3-chloro-3-oxopropanoate (0.13 mL, 90%, 1.0 mmol) was heated at 85° C. for 3 hours. Upon cooling to room temperature, dichloromethane and saturated aqueous sodium bicarbonate were added and the layers separated. The organic layer was washed with brine. The aqueous layers were extracted with dichloromethane and the combined organics dried over sodium sulfate. Filtration and concentration followed by silica gel chromatography provided methyl 3-{cyclopropyl[3-(ethyloxy)-3-oxopropanoyl]amino}-5-[(4-fluorophenyl)methyl]-2-pyridinecarboxylate (285 mg, 88%) as an oil.

Workup

  1. customthe layers separated
  2. washThe organic layer was washed with brine
  3. extractionThe aqueous layers were extracted with dichloromethane
  4. dry with materialthe combined organics dried over sodium sulfate
  5. filtrationFiltration and concentration

Sources & evidence

ORD record
ord-4dc7726931264c4d8ea68a22ff865ab1
Source dataset
uspto-grants-2014_04
Patent number
US08691991B2

Reaction notes

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