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

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.