Imidazole → HCID 90326879, compound

Participants

Reaction Steps

benzyl (3R,4R)-3,4-bis((tert-butyl(dimethyl)silyl)oxy)-1-piperidinecarboxylate and benzyl (3S,4S)-3,4-bis((tert-butyl(dimethyl)silyl)oxy)-1-piperidinecarboxylate (1/1). Benzyl 7-oxa-3-azabicyclo[4.1.0]heptane-3-carboxylate (5.00 g, 21.44 mmol, Bioorg. Med. Chem. Lett. 2007, 17, 1254) in 5% K2CO3 in 1/1 EtOH/H2O (214 mL) was heated at reflux for 3 h. After cooling to RT, the mixture was concentrated. EtOH (300 mL) was added to the liquid and removed in vacuo. The resulting solid was extracted with CHCl3 (2×250 mL). The combined CHCl3 fractions were dried over anh. Na2SO4, filtered and concentrated to give benzyl (3R,4R)-3,4-dihydroxy-1-piperidinecarboxylate and benzyl (3S,4S)-3,4-dihydroxy-1-piperidinecarboxylate (1/1) (5.98 g) as a light yellow syrup. MS (ESI, pos. ion) m/z: 252.1 [M+H]. A heterogenous mixture of benzyl (3R,4R)-3,4-dihydroxy-1-piperidinecarboxylate and benzyl (3S,4S)-3,4-dihydroxy-1-piperidinecarboxylate (1/1) (5.98 g, 23.80 mmol), tert-butyldimethylchlorosilane (10.76 g, 71.4 mmol) and imidazole (7.85 mL, 119 mmol) in DMF (24 mL) was stirred at RT overnight. H2O (300 mL) was added and the mixture was extracted with Et2O (3×100 mL). The combined organic layers were washed with H2O (300 mL) followed by brine (200 mL) and dried over anh. Na2SO4, filtered and concentrated. The crude material was purified by silica gel chromatography (0-20% EtOAc in hexanes) to provide benzyl (3R,4R)-3,4-bis((tert-butyl(dimethyl)silyl)oxy)-1-piperidinecarboxylate and benzyl (3S,4S)-3,4-bis((tert-butyl(dimethyl)silyl)oxy)-1-piperidinecarboxylate (1/1) (6.37 g, 13.28 mmol, 62% yield over two steps) as a clear, colorless oil. MS (ESI, pos. ion) m/z: 480.1 [M+H].

Provenance & Evidence