Ethyl-2-formylthiazole-4-carboxylate

Synthesis

General procedure for the synthesis of ethyl 2-formylthiazole-4-carboxylate from ethyl 2-(diethoxymethyl)thiazole-4-carboxylate: (v) Synthesis of ethyl 2-formylthiazole-4-carboxylate (see literature: Inami, K., Shiba, T., Bull. Chem. Soc. Jpn., 1985, 58, 352). Ethyl 2-(diethoxymethyl)thiazole-4-carboxylate (1.34 g, 5.17 mmol; see step (iv) above) was dissolved in acetone (100 mL) followed by addition of 1N HCl solution (12.8 mL). The reaction mixture was refluxed for 45 min, after which the solvent was removed by distillation under reduced pressure. The residue was dissolved in ethyl acetate (40 mL) and washed sequentially with saturated NaHCO3 solution (2 x 40 mL) and brine (2 x 40 mL). The organic phase was dried over anhydrous MgSO4, filtered and concentrated under reduced pressure to give ethyl 2-formylthiazole-4-carboxylate as a light brown solid (0.937 g, 98% yield). Melting point: 65-67°C (literature value: 67-68°C). IR (KBr, cm^-1): 3116 (Ar-H), 2983, 2910, 2814 (CH), 1730 (C=O), 1513 (C=N), 1060 (C-O). 1H NMR (CDCl3): δ 1.47 (3H, t, CH3, J = 8.0 Hz), 4.0%. 8.0 Hz), 4.50 (2H, q, CH2, J = 8.0 Hz), 8.52 (1H, d, Ar-H, J = 1.2 Hz), 10.08 (1H, d, Ar-CHO, J = 1.2 Hz).HRFABMS: measured value m/z 186.0228 (M + H), calculated value for CH7H7NO3S 185.0147.

References

[1] Bulletin of the Chemical Society of Japan, 1985, vol. 58, # 1, p. 352 - 360
[2] Organic and Biomolecular Chemistry, 2009, vol. 7, # 9, p. 1843 - 1850
[3] Patent: WO2008/38018, 2008, A1. Location in patent: Page/Page column 65
[4] Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 21, p. 6827 - 6843
[5] Synthetic Communications, 2012, vol. 42, # 14, p. 2098 - 2109