Ethyl Bromide → Ace-011

HRID 902446Notes

Reaction equation

HRID 902446 reaction equation
[C:1]([NH:4][C:5]1[CH:10]=[CH:9][C:8]([N+:11]([O-:13])=[O:12])=[CH:7][C:6]=1[OH:14])(=[O:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].[CH2:21](Br)[CH3:22].C(I)C>O.CN(C)C=O>[C:1]([NH:4][C:5]1[CH:10]=[CH:9][C:8]([N+:11]([O-:13])=[O:12])=[CH:7][C:6]=1[O:14][CH2:21][CH3:22])(=[O:3])[CH3:2]

Participants

7

Reactant 4

HCID 6332Ethyl Bromide2×HCID 6340Iodoethane2×HCID 11430Potassium CarbonateHCID 3749260N-(2-Hydroxy-4-nitrophenyl)acetamide3×

Product 1

HCID 2877953Ace-011Yield 98%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

A 12-L, 4-necked flask equipped with a reflux condenser, nitrogen inlet, thermocouple, addition funnel, and mechanical stirrer was charged with 400 g 2-Acetamido-5-nitrophenol. The flask was charged with 790 g potassium carbonate and 2.0 L of dimethylformamide (DMF). The mixture was stirred and warmed to 60±2.50° C. 294 g of ethyl bromide or ethyl iodide was added over 10 minutes to one hour while maintaining a 60° C. internal temperature. The reaction mixture was stirred for at least one hour or until the mixture turned yellow and the concentration of 2-Acetamido-5-nitrophenol was less than 1%, if needed additional ethyl bromide or ethyl iodide was added to reduce the concentration of 2-Acetamido-5-nitrophenol present. The mixture was cooled to 20±5° C. 4 L of water was added and while maintaining a 25±5° C. internal temperature. The suspension was stirred for a minimum of 30 minutes and collected by vacuum filtration. The product was washed and the pH monitored for a pH of <8. If the pH was >8, the product was washed with 1.0 L portions of warm water until the pH was <8. The resultant product was washed with heptane and vacuum dried. Yield 98%, strength 98.6%, mp 164-165° C.

Workup

  1. additionthermocouple, addition funnel, and mechanical stirrer
  2. temperaturewhile maintaining a 60° C. internal temperature
  3. stirringThe reaction mixture was stirred for at least one hour or until the mixture
  4. additionwas added
  5. temperatureThe mixture was cooled to 20±5° C
  6. temperaturewhile maintaining a 25±5° C. internal temperature
  7. stirringThe suspension was stirred for a minimum of 30 minutes
  8. filtrationcollected by vacuum filtration
  9. washThe product was washed
  10. washIf the pH was >8, the product was washed with 1.0 L portions of warm water until the pH was <8
  11. washThe resultant product was washed with heptane and vacuum
  12. customdried

Sources & evidence

ORD record
ord-6bcb98cb488d4b39b481fa3ef3ab34c4
Source dataset
uspto-grants-2008_04
Patent number
US07365203B2

Reaction notes

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