Acetyl chloride → Methyl 3-Amino-4-methoxybenzoate

HRID 1832067Notes

Reaction equation

HRID 1832067 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[O:11][CH3:12])[C:5]([OH:7])=[O:6].[C:13](Cl)(=O)C>CO>[NH2:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[O:11][CH3:12])[C:5]([O:7][CH3:13])=[O:6]

Participants

4

Reactant 2

HCID 6367Acetyl chlorideHCID 178233-Amino-4-methoxybenzoic acid

Product 1

HCID 2734814Methyl 3-Amino-4-methoxybenzoateYield 88.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A 1 L 3-necked round bottomed flask equipped with a nitrogen inlet, stirbar, addition funnel and thermocouple was charged with 3-amino-4-methoxy benzoic acid (50 g, 0.299 mol) and methanol (300 mL). The system was cooled to 0 C and acetyl choride (30 mL, 0.42 mol) was added dropwise. The system was warmed to room temperature, the addition funnel was replaced with a reflux condenser, and was heated to reflux for 1.5 h. The reaction mixture was cooled to room temperature, quenched with saturated aqueous NaHCO3, and extracted with ethyl acetate. The organic extract was washed with brine, dried with Na2SO4 and concentrated in vacuo to give methyl 3-amino-4-methoxybenzoate as a dark solid (47.9 g, 88%). 1H NMR (400 MHz, CD3OD) δ 7.40 (t, J=268 Hz, 1H), 7.37 (t, J=2.0 Hz, 1H), 6.86 (d, J=8.8 Hz, 1H), 3.98 (s, 3H), 3.81 (s, 3H) ppm. ES-HRMS m/z 182.0826 (M+H calcd for C9H12ClNO3 requires 182.0812). Step 2 Preparation of methyl 3-(4-hydroxy-6-methyl-2-oxopyridin-1(2H)-yl)-4-methoxybenzoate

Workup

  1. customA 1 L 3-necked round bottomed flask equipped with a nitrogen inlet
  2. additionstirbar, addition funnel
  3. additionwas added dropwise
  4. customthe addition funnel was replaced with a reflux condenser
  5. temperaturewas heated
  6. temperatureto reflux for 1.5 h
  7. temperatureThe reaction mixture was cooled to room temperature
  8. customquenched with saturated aqueous NaHCO3
  9. extractionextracted with ethyl acetate
  10. extractionThe organic extract
  11. washwas washed with brine
  12. dry with materialdried with Na2SO4
  13. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-edb55083d0614141b76ca169ab83de84
Source dataset
uspto-grants-2006_06
Patent number
US07067540B2

Reaction notes

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