Synthesis
General procedure for the synthesis of 4-bromotetrahydropyran from tetrahydropyran-4-ol:
A. Preparation of 4-bromotetrahydropyran. Tetrahydropyran-4-ol (1.0 g, 10 mmol), carbon tetrabromide (3.6 g, 11 mmol) and triphenylphosphine (3.1 g, 12 mmol) were dissolved in dichloromethane (25 mL) and the reaction was stirred at room temperature overnight. Upon completion of the reaction, the crude reaction mixture was concentrated and subsequently purified by rapid chromatography on silica gel (eluent ratio ethyl acetate:hexane = 1:20) to afford the target product 4-bromotetrahydropyran as a colorless oil (1.4 g, 87% yield).
References
[1] Journal of Medicinal Chemistry, 2017, vol. 60, # 7, p. 2780 - 2789
[2] Patent: WO2005/9973, 2005, A1. Location in patent: Page/Page column 85; 86
[3] Angewandte Chemie - International Edition, 2007, vol. 46, # 19, p. 3556 - 3558
[4] Justus Liebigs Annalen der Chemie, 1937, vol. 532, p. 80
[5] Chem.Abstr., 1940, p. 4396
