Synthesis
The general procedure for the synthesis of tetrahydropyran-4-carboxamide from methyl tetrahydropyran-4-carboxylate was as follows: tetrahydro-2H-pyran-4-carboxylic acid methyl ester (7 g, 48.6 mmol) was mixed with 30% ammonia (20 mL) in a closed reaction flask, and the reaction was stirred at room temperature for 18 hours. Upon completion of the reaction, the excess ammonia was removed by distillation under reduced pressure and the residue was recrystallized from ethanol to give 5.6 g (89% yield) of the target product, tetrahydro-2H-pyran-4-carboxamide. The structure of the product was confirmed by 1H NMR (401 MHz, DMSO-d6) with chemical shifts δ ppm of 7.21 (br.s, 1H), 6.73 (br.s, 1H), 3.90-3.80 (m, 2H), 3.30-3.23 (m, 2H), 2.36-2.24 (m, 1H), 1.66-1.47 (m, 4H ).
References
[1] Patent: WO2012/113774, 2012, A1. Location in patent: Page/Page column 41-42
[2] Patent: US2013/324551, 2013, A1. Location in patent: Paragraph 0326; 0327
[3] ChemMedChem, 2015, vol. 10, # 2, p. 276 - 295
[4] Patent: WO2015/62486, 2015, A1. Location in patent: Paragraph 00325
[5] Patent: US2007/111984, 2007, A1. Location in patent: Page/Page column 45
