(S)-Tetrahydro-2H-pyran-3-amine hydrochloride

Synthesis

General procedure for the synthesis of (S)-3-aminotetrahydropyran hydrochloride from the compound (CAS: 1295722-66-5): the intermediate (S)-tert-butyltetrahydro-2H-pyran-3-ylcarbamate (414 g, 2.06 mol) was added to a methanolic solution (4 L) of 6 N HCl, and the reaction mixture was stirred at room temperature until the reaction was complete (monitored by TLC monitoring). Upon completion of the reaction, the mixture was concentrated under vacuum to afford 283 g of (S)-(tetrahydropyran-3-yl)amine hydrochloride as a white solid (99.8% yield, enantiomeric excess >99%). The structure of the product was confirmed by 1H NMR (400 MHz, DMSO-d6): δ 8.37 (s, 3H), 3.87-3.72 (m, 1H), 3.70-3.57 (m, 1H), 3.54-3.38 (m, 2H), 3.12 (d, J = 2.1 Hz, 1H), 2.05-1.89 (m, 1H), 1.81 -1.60 (m, 2H), 1.49 (dtd, J = 12.5, 8.3, 4.3 Hz, 1H).

References

[1] Patent: WO2013/7768, 2013, A1. Location in patent: Page/Page column 110; 111
[2] Synlett, 2013, vol. 24, # 8, p. 987 - 990