Acetyl chloride → 4-[(Acetylphenylamino)-methyl]-1H-pyrrole-2-carboxylic acid ethyl ester

HRID 1366967Notes

Reaction equation

HRID 1366967 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[NH:7][CH:8]=[C:9]([CH2:11][NH:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:10]=1)=[O:5])[CH3:2].C(N(CC)C(C)C)(C)C.[C:28](Cl)(=[O:30])[CH3:29]>C(Cl)Cl>[CH2:1]([O:3][C:4]([C:6]1[NH:7][CH:8]=[C:9]([CH2:11][N:12]([C:28](=[O:30])[CH3:29])[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:10]=1)=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 6367Acetyl chlorideHCID 81531DiisopropylethylamineHCID 574351624-Phenylaminomethyl-1H-pyrrole-2-carboxylic acid ethyl ester

Product 1

HCID 574351644-[(Acetylphenylamino)-methyl]-1H-pyrrole-2-carboxylic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

4-Phenylaminomethyl-1H-pyrrole-2-carboxylic acid ethyl ester (183) (0.1523 g, 0.623 mmol) was weighed out into a 10 mL flask. A stir bar and septum were added, and the flask was purged with nitrogen. The amine was dissolved in methylene chloride (1.6 mL, 0.4 M) and then the flask was cooled to 0° C. N,N-diisopropyl ethyl amine (0.1194 mL, 0.686 mmol) was added, then acetyl chloride (0.0488 mL, 0.686 mmol) was added slowly by syringe to the stirring 0° C. solution. The reaction was then allowed to warm to room temperature. When the reaction was judged complete by HPLC (35 min) the reaction was diluted with methylene chloride and quenched with water. The organic phase was removed, washed with brine, dried with Na2SO4, filtered and concentrated en vacuo. The crude product was sufficiently pure by HPLC and NMR analysis that it was used in the next step without further purification (0.1625 g, 91%, white crystalline solid). 1H (CD3OD, 400 MHz): δ 11.22 (1H, broad s), 7.43-7.31 (3H, m), 7.08 (2H, dd, J=7.0, 1.5 Hz), 6.75 (1H, d, J=1.5 Hz), 6.68 (1H, d, J=1.5 Hz), 4.70 (2H, s), 4.24 (2H, q, J=7.0 Hz), 1.81 (3H, s), 1.31 (3H, t, J=7.0 Hz) ppm. 13C (CD3OD, 100 MHz): δ 172.47, 162.64, 143.86, 130.68, 129.34, 129.27, 124.50, 124.33, 122.19, 116.72, 61.16, 46.60, 22.64, 14.75 ppm. DEPT (CD3OD, 100 MHz): CH3 carbons: 22.64, 14.75; CH2 carbons: 61.16, 46.60; CH carbons: 130.68, 129.34, 129.27, 124.33, 116.72 ppm. HPLC: 8.738 min.

Workup

  1. additionA stir bar and septum were added
  2. customthe flask was purged with nitrogen
  3. dissolutionThe amine was dissolved in methylene chloride (1.6 mL, 0.4 M)
  4. temperatureto warm to room temperature
  5. customwas judged complete by HPLC (35 min)
  6. customquenched with water
  7. customThe organic phase was removed
  8. washwashed with brine
  9. dry with materialdried with Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated en vacuo
  12. customwas used in the next step without further purification (0.1625 g, 91%, white crystalline solid)
  13. custom8.738 min.

Sources & evidence

ORD record
ord-689b9497fc024b2ea76d086bafca9093
Source dataset
uspto-grants-2011_02
Patent number
US07893098B2

Reaction notes

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