(3aS)-1-methyl-3,3-diphenyl-hexahydropyrrolo(1,2-c)(1,3,2)oxazaborole → (R)-tert-butyl 4-((5-hydroxyhexyl)oxy)-4-methylpiperidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a stirred yellow solution of tert-butyl 4-methyl-4-((5-oxohexyl)oxy)piperidine-1-carboxylate (5.8 g, 18.50 mmol) in anhydrous toluene (100 mL) was added (S)-1-methyl-3,3-diphenylhexahydropyrrolo[1,2-c][1,3,2]oxazaborole (2.052 g, 7.40 mmol). The mixture was cooled to −35° C. and a solution of 50% catechoborane (6.35 mL, 25.9 mmol) in toluene was added over 5 min. After 30 min, the reaction mixture was slowly warmed to −15° C. and stirred for additional 2 h. At his point LCMS indicated completion of reaction. Mixture was then diluted with EtOAc (200 mL) and sat. Na2CO3 (100 mL). The mixture was stirred vigorously for 30 min, and the organic phase washed with sat Na2CO3 (2×50 mL), dried (Na2SO4), filtered, concentrated and the residue was purified by silica gel chromatography (5-70% EtOAc/hexane) to afford desired (R)-tert-butyl 4-((5-hydroxyhexyl)oxy)-4-methylpiperidine-1-carboxylate (4.6 g, 14.58 mmol, 79% yield) as colorless oil. 1H NMR (500 MHz, CDCl3) δ 3.90-3.80 (m, 1H), 3.78-3.64 (m, 2H), 3.33 (t, J=6.4 Hz, 2H), 3.14 (t, J=11.4 Hz, 2H), 1.74 (d, J=13.2 Hz, 2H), 1.66-1.54 (m, 3H), 1.53-1.46 (m, 12H), 1.46-1.38 (m, 3H), 1.22 (d, J=6.3 Hz, 3H), 1.17 (s, 3H). LCMS (M+Na)=338.4.

Provenance & Evidence