| 90% |
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General procedure: To a stirred solution of the substituted 1H-Pyrrole-3-carboxylicacid (765 mg, 5 mmol,) in dry DMF, NaH (300 mg, 7.5 mmol) was added in portions under air at 0 C. The reaction mixture was then warmed to room temperature and stirred for 30 mins. After cooling to 0 C again, MeI (1.06 g, 7.5 mmol) was added dropwise. The reaction mixture was warmed to room temperature again and stirred overnight. The reaction mixture was quenched with water, and the aqueous layer was extracted with ether. The combined organic layer was washed with brine, dried over anhydrous Na2SO4, and concentrated under vacuum. The residue was purified by flash column chromatography (petroleum ether/ethyl acetate = 5:1) to give compound as colorless solid (751 mg, 90% yield). 3c: 1 H NMR (400 MHz, CDCl 3 ) delta 6.50 (d, J = 2.8 Hz, 1H), 6.46 (d, J = 2.8 Hz, 1H), 4.25 (q, J = 6.8 Hz, 2H), 3.52 (s, 3H), 2.50 (s, 3H), 1.33 (t, J = 6.8 Hz, 3H). 13 C NMR (101 MHz, CDCl 3 ) delta 165.7, 136.0, 120.9, 112.3, 109.3, 59.3, 33.9, 14.6, 11.0. HRMS ESI (m/z): [M+H] + calcd. for C 9 H 14 NO 2 : 168.1025, found: 168.1024. |
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With sodium hydride; In N,N-dimethyl-formamide; mineral oil; at 0℃; for 1h; |
a) 1,2-Dimethyl-1H-pyrrole-3-carboxylic acid ethyl ester To a mixture of <strong>[936-12-9]2-methyl-1H-pyrrole-3-carboxylic acid ethyl ester</strong> (7.1 g, 46.05 mmol), iodomethane (5.73 mL, 92.1 mmol) in DMF (50 mL) at 0 C. was added sodium hydride (NaH) (2.39 g, 59.9 mmol, 60% in mineral oil) in one portion, the mixture was stirred at 0 C. for 1 h then the mixture was poured into ice-water (300 mL), extracted with EtOAc, the organic phase was washed with diluted HCl aqueous solution, water and saturated NaCl aqueous solution respectively; the EtOAc layer was then dried over anhydrous sodium sulfate, filtered, concentrated, the residue was purified with column to give a colorless oil, the desired title compound (3.25 g); 1H NMR (200 MHz, CDCl3): delta (ppm)=6.5-6.4 (m, 2H), 4.24 (q, 2H, J=7.1 Hz), 3.52 (s, 3H), 2.49 (s, 3H), 1.33 (t, 3H, J=7.1 Hz). |
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With sodium hydride; In N,N-dimethyl-formamide; mineral oil; at 0℃; for 1h; |
Step A: Ethyl 1,2-dimethyl-1H-pyrrole-3-carboxylate To a solution of 10 g of <strong>[936-12-9]ethyl 2-methyl-1H-pyrrole-3-carboxylate</strong> (65.3 mmol) and 8.95 mL (130.6 mmol) of methyl iodide in 70 mL of dimethylformamide placed at 0 C. there are added, in three portions, 2.61 g (65.3 mmol) of sodium hydride 60%. The batch is then stirred at 0 C. for 1 hour. Then, the reaction mixture is hydrolysed by the addition of 420 mL of ice-cold water. The reaction mixture is then diluted with ethyl acetate, successively washed with 0.1M HCl solution, saturated aqueous LiCl solution and then brine. The organic phase is then dried over MgSO4, filtered, concentrated to dryness and purified by chromatography over silica gel (petroleum ether/AcOEt gradient). 1H NMR: delta (400 MHz; dmso-d6; 300K): 6.65 (d, 1H pyrrole); 6.3 (Id, 1H pyrrole); 4.1 (1q, 2H, OCH2CH3); 3.5 (s, 3H N-pyrrole); 2.4 (s, 3H pyrrole); 1.5 (it, 3H OCH2CH3) IR: nu: >C=O: 1688 cm-1; nu: C-O-C: 1172 cm-1 |
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