Water → Ethyl 4,5-dimethyl-1-(quinolin-4-yl)-1H-pyrrole-3-carboxylate

HRID 1792813Notes

Reaction equation

HRID 1792813 reaction equation
[H-].[Na+].[CH2:3]([O:5][C:6]([C:8]1[C:12]([CH3:13])=[C:11]([CH3:14])[NH:10][CH:9]=1)=[O:7])[CH3:4].Cl[C:16]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[N:19]=[CH:18][CH:17]=1.O>CN(C)C=O>[CH2:3]([O:5][C:6]([C:8]1[C:12]([CH3:13])=[C:11]([CH3:14])[N:10]([C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[N:19]=[CH:18][CH:17]=2)[CH:9]=1)=[O:7])[CH3:4]

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 691404-ChloroquinolineHCID 1374834,5-Dimethyl-1H-pyrrole-3-carboxylic acid ethyl ester

Product 1

HCID 22024966Ethyl 4,5-dimethyl-1-(quinolin-4-yl)-1H-pyrrole-3-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
40 °C

Procedure

0.285 g (8.9 mmol) of sodium hydride, at 75% by weight in liquid petroleum jelly, is added at a temperature in the region of 20° C. under an argon atmosphere to a solution of 1.35 g (8.1 mmol) of 3-ethoxycarbonyl-4,5-dimethyl-1H-pyrrole in 8 mL of dimethylformamide. After stirring at a temperature in the region of 40° C. for 0.3 hour, 1.45 g (8.9 mmol) of 4-chloroquinoline and 2 mL of dimethylformamide are added. After stirring at a temperature in the region of 140° C. for 6 hours, the reaction mixture is poured into 100 mL of salt water and then extracted with twice 50 mL of ethyl acetate. The combined organic phases are washed with 15 mL of water, carefully separated by settling and then concentrated to dryness under reduced pressure (2.7 kPa) to give a brown oil which is purified by silica gel chromatography [eluent: cyclohexane/ethyl acetate (75/25 by volume)]. After concentrating the fractions under reduced pressure (2.7 kPa), 1.32 g of 3-ethoxycarbonyl-4,5-dimethyl-1-(quinol-4-yl)-1H-pyrrole are obtained in the form of a yellowish oil. 1H NMR spectrum (300 MHz, d6-(CD3)2SO, δ in ppm): 1.27 (t, J=7 Hz, 3H), 1.87 (s, 3H), 2.27 (s, 3H), 4.21 (mt, 2H), 7.37 (dd, J=8 and 1 Hz, 1H), 7.55 (s, 1H), 7.62 (d, J=5 Hz, 1H), 7.70 (ddd, J=8, 7 and 1 Hz, 1H), 7.89 (ddd, J=8, 7 and 1 Hz, 1H), 8.19 (broad d, J=8 Hz, 1H), 9.07 (d, J=5 Hz, 1H).

Workup

  1. stirringAfter stirring at a temperature in the region of 140° C. for 6 hours
  2. extractionextracted with twice 50 mL of ethyl acetate
  3. washThe combined organic phases are washed with 15 mL of water
  4. customcarefully separated
  5. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  6. customto give a brown oil which
  7. customis purified by silica gel chromatography [eluent: cyclohexane/ethyl acetate (75/25 by volume)]
  8. concentrationAfter concentrating the fractions under reduced pressure (2.7 kPa), 1.32 g of 3-ethoxycarbonyl-4,5-dimethyl-1-(quinol-4-yl)-1H-pyrrole
  9. customare obtained in the form of a yellowish oil

Sources & evidence

ORD record
ord-e151ce452e1241aabb17de853cb0412b
Source dataset
uspto-grants-2006_07
Patent number
US07078414B2

Reaction notes

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