Aniline → 4-Phenylaminomethyl-1H-pyrrole-2-carboxylic acid ethyl ester

HRID 1434819Notes

Reaction equation

HRID 1434819 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[NH:7][CH:8]=[C:9]([CH:11]=O)[CH:10]=1)=[O:5])[CH3:2].[NH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C([BH3-])#N.[Na+].C([O-])([O-])=O.[K+].[K+]>C(O)(=O)C.CO>[CH2:1]([O:3][C:4]([C:6]1[NH:7][CH:8]=[C:9]([CH2:11][NH:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:10]=1)=[O:5])[CH3:2]

Participants

7

Reactant 4

HCID 6115AnilineHCID 11430Potassium CarbonateHCID 321486Ethyl 4-formyl-1H-pyrrole-2-carboxylateHCID 5003444Sodium cyanoborohydride

Product 1

HCID 574351624-Phenylaminomethyl-1H-pyrrole-2-carboxylic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 887MethanolSolvent

Procedure

0.2012 g (1.20 mmol) of 4-formyl-1H-pyrrole-2-carboxylic acid ethyl ester was dissolved in 4.8 mL (0.25 M) of 5% acetic acid in methanol. Aniline (0.13 mL g, 1.44 mmol) was added, and the reaction was stirred at room temperature under nitrogen for 45 minutes, then sodium cyanoborohydride (0.1244 g, 1.98 mmol) was added slowly and the reaction was allowed to stir at room temperature overnight. About 2 mL of saturated K2CO3 were added, and the reaction was extracted twice with ethyl acetate. The combined organics were washed with saturated NaHCO3 (˜3 mL) and brine (˜3 mL), then the combined organics were dried with Na2SO4, filtered and concentrated en vacuo. The crude product was purified by silica gel chromatography (Combiflash column, 85:15 Hexanes:Ethyl acetate) to obtain 0.2663 g (91%) of 4-phenylaminomethyl]-1H-pyrrole-2-carboxylic acid ethyl ester (183) as a colorless viscous oil. Note: Starting material 4-formyl-1H-pyrrole-2-carboxylic acid ethyl ester has an HPLC retention time=7.337 min. 1H (CDCl3, 400 MHz): 89.49 (1H, broad s), 7.19 (2H, dd, J=8.6, 7.3 Hz), 6.73 (1H, tt, J=7.3, 1.1 Hz), 6.66 (2H, dd, J=8.6, 1.1 Hz), 6.91 (1H, d, J=2.0 Hz), 6.90 (1H, d, J=2.0 Hz), 4.33 (2H, q, J=7.2 Hz), 4.19 (2H, s), 3.90 (1H, broad s), 1.36 (3H, t, J=7.2 Hz) ppm. HPLC: 6.936 min.

Workup

  1. stirringto stir at room temperature overnight
  2. extractionthe reaction was extracted twice with ethyl acetate
  3. washThe combined organics were washed with saturated NaHCO3 (˜3 mL) and brine (˜3 mL)
  4. dry with materialthe combined organics were dried with Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated en vacuo
  7. customThe crude product was purified by silica gel chromatography (Combiflash column, 85:15 Hexanes:Ethyl acetate)

Sources & evidence

ORD record
ord-b6a9ca0409b945fabaa037d91f5f16df
Source dataset
uspto-grants-2009_11
Patent number
US07615572B2

Reaction notes

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