Acetyl chloride → HCID 57561744, compound

HRID 1366969Notes

Reaction equation

HRID 1366969 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][C:16]([Cl:19])=[CH:15][CH:14]=2)[CH:10]=1)=[O:5])[CH3:2].C(N(CC)C(C)C)(C)C.[C:29](Cl)(=[O:31])[CH3:30]>C(Cl)Cl>[CH2:1]([O:3][C:4]([C:6]1[NH:7][CH:8]=[C:9]([CH2:11][N:12]([C:29](=[O:31])[CH3:30])[C:13]2[CH:14]=[CH:15][C:16]([Cl:19])=[CH:17][CH:18]=2)[CH:10]=1)=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 6367Acetyl chlorideHCID 81531DiisopropylethylamineHCID 57435166HCID 57435166, compound

Product 1

HCID 57561744HCID 57561744, compoundYield 82%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

4-[(4-chlorophenylamino)-methyl]-1H-pyrrole-2-carboxylic acid ethyl ester (187) (0.2868 g, 1.03 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 (2.6 mL, 0.4 M) and then the flask was cooled to 0° C. N,N-diisopropyl ethyl amine (0.1971 mL, 1.13 mmol) was added, then acetyl chloride (0.0805 mL, 1.13 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 (90 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 purified by silica gel chromatography (Combiflash column, 2:1 Hexanes:Ethyl acetate) to obtain pure 4-[(acetyl-(4-chlorophenyl)-amino)-methyl]-1H-pyrrole-2-carboxylic acid ethyl ester (189, 0.2701 g, 82%) as a sticky white solid. 1H (CD3OD, 400 MHz): δ 11.25 (1H, broad s), 7.35 (2H, d, J=8.4 Hz), 7.05 (2H, d, J=8.4 Hz), 6.76 (1H, s), 6.69 (1H, s), 4.68 (2H, s), 4.22 (2H, q, J=7.1 Hz), 1.81 (3H, s), 1.29 (3H, t, J=7.1 Hz) ppm. 13C (CD3OD, 100 MHz): δ 172.17, 162.50, 142.39, 134.87, 130.94, 130.70, 124.46 & 124.30, 123.94, 121.91 & 121.88, 116.64, 61.13, 46.43, 22.70, 14.75 ppm. DEPT (CD3OD, 100 MHz): CH3 carbons: 22.70, 14.75; CH2 carbons: 61.13, 46.43; CH carbons: 130.94, 130.70, 124.46 & 124.30, 116.64 ppm. HPLC: 9.247 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 (2.6 mL, 0.4 M)
  4. temperatureto warm to room temperature
  5. customwas judged complete by HPLC (90 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. customThe crude product was purified by silica gel chromatography (Combiflash column, 2:1 Hexanes:Ethyl acetate)

Sources & evidence

ORD record
ord-e87f781daf7b412f912c703da519f857
Source dataset
uspto-grants-2011_02
Patent number
US07893098B2

Reaction notes

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