Synthesis
1. Add N,N-dimethylformamide (8.54 g, 117 mmol) and ethylene dichloride (120 mL) to a 250 mL three-necked round-bottomed flask fitted with a magnetic stir bar.
2. Phosphoryl chloride (17.9 g, 117 mmol) was added slowly and dropwise with stirring at 0 °C. The reaction was carried out by stirring.
3. Stir the reaction mixture at room temperature for 15 min.
4. 2-methylpyrrole (10.0 g, 123 mmol) was added slowly and dropwise, keeping the reaction temperature at 0 °C.
5. The reaction mixture was warmed to 80 °C and stirred for 30 min.
6. An aqueous solution (130 mL) of sodium acetate (46 g, 561 mmol) was added to the reaction mixture at room temperature.
7. The reaction mixture was stirred at 80 °C for 20 minutes and then cooled to room temperature.
8. The reaction was quenched with water (100 mL).
9. The reaction mixture was extracted with dichloromethane (3 x 250 mL) and the organic layers were combined.
10. The organic layer was washed with saturated aqueous sodium bicarbonate (150 mL).
11. The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated in vacuum.
12. The residue was purified by column chromatography with the eluent ethyl acetate/hexane (1:5 v/v) to afford 5-methylpyrrole-2-carbaldehyde (7.50 g, 56% yield).
13. LCMS (ESI) m/z 110 [M + H].
References
[1] Organic Letters, 2006, vol. 8, # 21, p. 4951 - 4954
[2] Tetrahedron, 1993, vol. 49, # 7, p. 1343 - 1350
[3] Patent: US2016/185786, 2016, A1. Location in patent: Paragraph 0606
[4] Journal of Organic Chemistry, 1980, vol. 45, # 24, p. 4980 - 4982
[5] Journal of Medicinal Chemistry, 2004, vol. 47, # 16, p. 4054 - 4059
