Triethylamine → Acetic acid 4-acryloylamino-phenyl ester

HRID 1970754Notes

Reaction equation

HRID 1970754 reaction equation
[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([O:10][C:11](=[O:13])[CH3:12])=[CH:6][CH:5]=1)([O-])=O.C(N(CC)CC)C.[C:21](Cl)(=[O:24])[CH:22]=[CH2:23]>CO.C(Cl)Cl.[Pd]>[C:21]([NH:1][C:4]1[CH:9]=[CH:8][C:7]([O:10][C:11](=[O:13])[CH3:12])=[CH:6][CH:5]=1)(=[O:24])[CH:22]=[CH2:23]

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 13140Acryloyl chlorideHCID 132434-Nitrophenyl Acetate

Product 1

HCID 69041419Acetic acid 4-acryloylamino-phenyl esterYield 85%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

H2 is bubbled through a solution of 1 (280 mg, 1.54 mmol) and 10 mg of 10% Pd on carbon in 20 ml of MeOH for 1 hr. The catalyst is removed by filtration. Triethylamine (410 μl, 3.08 mmol) is added to the filtrate which was chilled on ice, then acryloyl chloride (250 μl, 3.08 mmol, Aldrich) in 10 ml of dry CH2Cl2 is added dropwise with stirring over 0.5 hr under Ar. The reaction is then allowed to return to ambient temperature, followed by 2 hr of stirring. Anion exchange resin (Bio-Rad, AG-MP1, OH−) (4 equivalents based on acryloyl chloride) is added, the mixture is filtered, and the filtrate is treated with sufficient cation exchange resin (Dowex, 50W×8, H+) to bring the mixture to neutrality (moist pH paper). The resin is removed by filtration, and the solvent is removed by rotary evaporation to yield an off-white solid (268 mg, 85%). ESI-MS (M+H)+: 206.1. 1H-NMR (acetone-d6) δ 9.15 (1H, br, NH), 7.78 (2H, d, J=9.0 Hz, NHCCH), 7.08 (2H, d, J=9.0 Hz, NHCCHCH), 6.55˜6.37 (2H, m, COCHCHH (anti to each other)), 5.75 (1H, dd, J=9.8 and 2.2 Hz, COCHCHH (syn to COCH)), 2.25 (3H, s, CH3).

Workup

  1. customThe catalyst is removed by filtration
  2. temperaturewas chilled on ice
  3. customto return to ambient temperature
  4. waitfollowed by 2 hr
  5. stirringof stirring
  6. additionAnion exchange resin (Bio-Rad, AG-MP1, OH−) (4 equivalents based on acryloyl chloride) is added
  7. filtrationthe mixture is filtered
  8. additionthe filtrate is treated with sufficient cation exchange resin (Dowex, 50W×8, H+)
  9. customThe resin is removed by filtration
  10. customthe solvent is removed by rotary evaporation

Sources & evidence

ORD record
ord-f69e63c126a64994960c3a18f585838b
Source dataset
uspto-grants-2013_04
Patent number
US08431335B2

Reaction notes

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