ChemicalBook CAS DataBase List 1H-Pyrrole-2-carboxylicacid,5-cyano-,methylester(9CI)

1H-Pyrrole-2-carboxylicacid,5-cyano-,methylester(9CI) synthesis

8synthesis methods

Product Name:1H-Pyrrole-2-carboxylicacid,5-cyano-,methylester(9CI)
CAS Number:937-19-9
Molecular formula:C7H6N2O2
Molecular Weight:150.13

5-Formylpyrrole-2-carboxylic acid methyl ester

1197-13-3

1H-Pyrrole-2-carboxylicacid,5-cyano-,methylester(9CI)

937-19-9

General procedure for the synthesis of methyl 5-cyano-1H-pyrrole-2-carboxylate from methyl 5-formyl-1H-pyrrole-2-carboxylate: NH2OH-HCl (0.58 g, 8.4 mmol) and NaOAc (0.63 g, 7.6 mmol) were added to an 5-formyl-1H-pyrrole-2-carboxylic acid methyl ester (1.14 g, 7.6 mmol) in an anhydrous MeOH solution (8 mL). The reaction mixture was heated at reflux temperature for 1 hour. Upon completion of the reaction, the reaction was quenched with aqueous NaHCO3 and the aqueous layer was extracted three times with CH2Cl2. The organic layers were combined, dried with anhydrous MgSO4 and concentrated in vacuum to give the corresponding aldoxime (1.11 g, 87% yield). The crude aldoxime (5.8 g, 34 mmol) was dissolved in anhydrous N,N-dimethylformamide (DMF, 28 mL) and POCl3 (8.4 g, 55 mmol) was added dropwise to the solution at -20 °C. After stirring for 30 minutes at -20°C, the solution was brought to room temperature and continued to stir for 2 hours. After completion of the reaction, the reaction was quenched with water and the aqueous layer was extracted three times with CH2Cl2. The organic layers were combined, washed five times with water, dried over anhydrous MgSO4, and concentrated in vacuum to afford methyl 5-cyano-1H-pyrrole-2-carboxylate (4.2 g, 71% yield) as a colorless solid (mp = 173.7-174.8 °C) with an Rf of 0.23 (hexane/ethyl acetate = 3:1).1H NMR (400 MHz, CDCl3) δ 9.92 ( br, 1H), 6.89 (dd, J = 3.9,2.5 Hz, 1H), 6.84 (dd, J = 4.0,2.6 Hz, 1H), 3.94 (s, 3H); 13C NMR (101 MHz, CDCl3) δ160.9,126.7,120.1,115.2,112.8,105.7,52.7; HRMS (EI) calculated value C7H6N2O2: [M]+, 150.0429. measured value: m/z 150.0430.

1197-13-3
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937-19-9
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Yield:937-19-9 71%

Reaction Conditions:

Stage #1: methyl 5-formyl-1H-pyrrole-2-carboxylatewith AMINOHIPPURATE SODIUM;hydroxylamine hydrochloride in methanol; for 1 h;Reflux;
Stage #2: with trichlorophosphate in N,N-dimethyl-formamide at -20 - 20; for 2.5 h;

Steps:

2 3.2
Methyl 5-cyano-1H-pyrrole-2-carboxylate (4)

NH₂OH·HCl (0.58 g, 8.4 mmol) and NaOAc (0.63 g, 7.6 mmol) were added to a solution of methyl 5-formyl-1H-pyrrole-2-carboxylate
¹²
(1.14 g, 7.6 mmol) in anhydrous MeOH (8 mL), and the mixture was heated at the reflux temperature for 1 h.
The resulting solution was quenched with NaHCO₃ aq, and the aqueous layer was extracted with CH₂Cl₂ for three times.
The combined organic layers were dried over anhydrous MgSO₄ and concentrated in vacuo to give the corresponding aldoxime (1.11 g, <87%).
The crude oxime (5.8 g, 34 mmol) thus obtained was dissolved in anhydrous N,N-dimethylformamide (DMF, 28 mL), and the solution was added dropwise POCl₃ (8.4 g, 55 mmol) at -20 °C.
After being stirred for 30 min at -20 °C and then at rt for 2 h, the reaction was quenched with water.
The aqueous layer was extracted with CH₂Cl₂ for three times.
The combined organic layers were washed with water for five times, dried over anhydrous MgSO₄, and concentrated in vacuo to give the title compound (4.2 g, ～71%) as a colorless solid (mp=173.7-174.8 °C), R_f 0.23 (hexane/ethyl acetate=3:1).
¹H NMR (400 MHz, CDCl₃) δ 9.92 (br, 1H), 6.89 (dd, J=3.9, 2.5 Hz, 1H), 6.84 (dd, J=4.0, 2.6 Hz, 1H), 3.94 (s, 3H); ¹³C NMR (101 MHz, CDCl₃) δ 160.9, 126.7, 120.1, 115.2, 112.8, 105.7, 52.7; HRMS (EI) calcd for C₇H₆N₂O₂: M⁺, 150.0429. Found: m/z 150.0430.