Acryloyl chloride → Methyl 4-Acryloylamino-5-chloro-2-methoxybenzoate

HRID 407128Notes

Reaction equation

HRID 407128 reaction equation
[NH2:1][C:2]1[C:11]([Cl:12])=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([O:13][CH3:14])[CH:3]=1.C(N(C(C)C)CC)(C)C.[C:24](Cl)(=[O:27])[CH:25]=[CH2:26].C(=O)(O)[O-].[Na+]>ClCCl>[C:24]([NH:1][C:2]1[C:11]([Cl:12])=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([O:13][CH3:14])[CH:3]=1)(=[O:27])[CH:25]=[CH2:26]

Participants

6

Reactant 4

HCID 13140Acryloyl chlorideHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 700493Methyl 4-amino-5-chloro-2-methoxybenzoate

Product 1

HCID 21880616Methyl 4-Acryloylamino-5-chloro-2-methoxybenzoateYield 67%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a 1-liter three-necked round-bottom flask equipped with overhead stirrer, temperature control and addition funnel was added methyl 4-amino-5-chloro-2-methoxybenzoate (44.2 g, 200 mmol), dichloromethane (500 mL) and diisopropylethylamine (104.5 mL, 600 mmol). The resulting mixture was stirred at room temperature until the ingredients dissolved and then the mixture was cooled to 0° C. Acryloyl chloride (16.25 mL, 200 mmol) was then added dropwise while maintaining the internal reaction mixture temperature below 10° C. The total time for addition was about 30 min. The reaction mixture was then slowly warmed from 0° C. to room temperature over a period of about 2 hours. Aqueous saturated sodium bicarbonate solution (200 mL) and dichloromethane (200 mL) were then added and this mixture was stirred for 15 min. and then the layers were separated. The dichloromethane layer was washed with 1 M hydrochloric acid (200 mL) and then concentrated under reduced pressure to about one-third its original volume resulting in a thick slurry. The slurry was filtered and the filter cake was washed with dichloromethane (100 mL) and dried to provide the title compound as an off-white solid (36 g, 67% yield, >98% purity by HPLC).

Workup

  1. customTo a 1-liter three-necked round-bottom flask equipped with overhead stirrer
  2. additiontemperature control and addition funnel
  3. dissolutiondissolved
  4. temperaturethe mixture was cooled to 0° C
  5. temperaturewhile maintaining the internal reaction mixture temperature below 10° C
  6. additionThe total time for addition
  7. temperatureThe reaction mixture was then slowly warmed from 0° C. to room temperature over a period of about 2 hours
  8. stirringthis mixture was stirred for 15 min.
  9. customthe layers were separated
  10. washThe dichloromethane layer was washed with 1 M hydrochloric acid (200 mL)
  11. concentrationconcentrated under reduced pressure to about one-third its original volume
  12. customresulting in a thick slurry
  13. filtrationThe slurry was filtered
  14. washthe filter cake was washed with dichloromethane (100 mL)
  15. customdried

Sources & evidence

ORD record
ord-89574fdd6e744409a0eaf5f0e5795212
Source dataset
uspto-grants-2014_06
Patent number
US08754223B2

Reaction notes

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