Potassium Carbonate → Methyl (2-chloro-4-cyano-5-methoxyphenyl)acetate

HRID 1186994Notes

Reaction equation

HRID 1186994 reaction equation
[CH3:1][O:2][C:3](=[O:15])[CH2:4][C:5]1[CH:10]=[C:9](F)[C:8]([C:12]#[N:13])=[CH:7][C:6]=1[Cl:14].[C:16](=O)([O-])[O-:17].[K+].[K+]>CO>[CH3:1][O:2][C:3](=[O:15])[CH2:4][C:5]1[CH:10]=[C:9]([O:17][CH3:16])[C:8]([C:12]#[N:13])=[CH:7][C:6]=1[Cl:14]

Participants

4

Reactant 2

HCID 11430Potassium CarbonateHCID 90882704Methyl (2-chloro-4-cyano-5-fluorophenyl)acetate

Product 1

HCID 77231255Methyl (2-chloro-4-cyano-5-methoxyphenyl)acetate

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
130 °C

Procedure

A solution of methyl(2-chloro-4-cyano-5-fluorophenyl)acetate (1.40 g, 6.15 mmol) in methanol (30 mL) was divided into two 20 mL microwave vials. Potassium carbonate (2×850 mg) was added to each vial. Each was heated in a microwave at 130° C. for 60 minutes at which time HPLC/MS indicated no starting material was left and the product was all hydrolyzed to the acid. Most of the methanol was removed in vacuo and the residue was diluted with water, acidified with 2M HCl and the mixture was extracted twice with ethyl acetate. The organic layers were washed with brine, dried over sodium sulfate and concentrated in vacuo. The crude product was taken up in 1:1 methanol:dichloromethane (50 mL) and 2M trimethylsilyldiazomethane in ether was added until the yellow color persisted to re-esterify the acid. The excess diazomethane was quenched with acetic acid and the mixture was concentrated. Flash chromatography (40% DCM/hexanes to 100% DCM) gave the methyl(2-chloro-4-cyano-5-methoxyphenyl)acetate. 1H-NMR (400 MHz, CDCl3) δ ppm 3.73 (s, 3H), 3.83 (s, 2H), 4.07 (s, 3H), 7.139 (d, J=8.1 Hz, 1H), 7.468 (d, J=8.0, 1H).

Workup

  1. waitwas left
  2. customMost of the methanol was removed in vacuo
  3. additionthe residue was diluted with water
  4. extractionthe mixture was extracted twice with ethyl acetate
  5. washThe organic layers were washed with brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated in vacuo
  8. additiondichloromethane (50 mL) and 2M trimethylsilyldiazomethane in ether was added until the yellow color
  9. customThe excess diazomethane was quenched with acetic acid
  10. concentrationthe mixture was concentrated

Sources & evidence

ORD record
ord-b3a0dd0c75c84d0bbaf93ea1aa2e1a08
Source dataset
uspto-grants-2014_03
Patent number
US08673920B2

Reaction notes

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