Sodium hydride → 3-(Ethoxycarbonyl)-4-(4-methylphenyl)pyrrole

HRID 1921566Notes

Reaction equation

HRID 1921566 reaction equation
CC1C=CC(S([CH2:11][N+:12]#[C-:13])(=O)=O)=CC=1.[CH2:14]([O:16][C:17](=[O:27])[CH:18]=[CH:19][C:20]1[CH:25]=[CH:24][C:23]([CH3:26])=[CH:22][CH:21]=1)[CH3:15].CCOCC.CS(C)=O.[H-].[Na+]>CCOCC.O>[CH2:14]([O:16][C:17]([C:18]1[C:19]([C:20]2[CH:21]=[CH:22][C:23]([CH3:26])=[CH:24][CH:25]=2)=[CH:13][NH:12][CH:11]=1)=[O:27])[CH3:15]

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 161915Tosylmethyl isocyanideHCID 334099Ethyl 3-(4-methylphenyl)-2-propenoateHCID 19869614Ether dimethylsulfoxide

Product 1

HCID 674921883-(Ethoxycarbonyl)-4-(4-methylphenyl)pyrroleYield 74.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3283Diethyl EtherSolvent

Procedure

A solution of TosMIC (15.7 g, 80.5 mmol) and 5 (14.6 g, 76.7 mmol) in a dry ether/DMSO (2:1) (154 mL) solution was added dropwise under argon to a stirred solution of NaH (2.39 g, 99.7 mmol) in ether (70 mL). The mixture started to reflux due to the exothermic reaction. After 3 h, water (200 mL) was carefully added to the mixture and the aqueous phase was extracted with ether and CH2Cl2. The combined organic extracts were dried (Na2SO4), concentrated, and chromatographed [silica, CH2Cl2/ethyl acetate (9:1)] to give a light brown solid (13.1 g, 74%): mp 154-155° C.; 1H NMR δ 1.25 (t, J=7.2 Hz, 3H), 2.36 (s, 3H), 4.22 (q, J=7.2 Hz, 2H), 6.75-6.77 (m, 1H), 7.16 (d, J=7.8 Hz, 2H), 7.38 (d, J=7.8 Hz, 2H), 7.40-7.48 (m, 1H), 8.38-8.54 (br, 1H); 13C NMR δ 14.5, 21.4, 59.8, 113.9, 118.3, 125.4, 126.8, 128.6, 129.4, 132.0, 136.3, 165.2; Anal. Calcd for C14H15NO2: C, 73.34; H, 6.59; N, 6.11. Found: C, 73.11; H, 6.59; N, 6.12.

Workup

  1. temperatureto reflux due to the exothermic reaction
  2. extractionthe aqueous phase was extracted with ether and CH2Cl2
  3. dry with materialThe combined organic extracts were dried (Na2SO4)
  4. concentrationconcentrated
  5. customchromatographed [silica, CH2Cl2/ethyl acetate (9:1)]

Sources & evidence

ORD record
ord-20b05d83523041109482226f11dbc324
Source dataset
uspto-grants-2012_05
Patent number
US08173692B2

Reaction notes

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