Reaction Steps
A sample of benzyl (1S,2R,4R)-4-hydroxy-2-(hydroxymethyl)cyclohexylcarbamate (20.5 g, 73.4 mmol) was dissolved in anhydrous pyridine (140 mL) at room temperature prior to the addition of trityl chloride (20.46 g, 73.4 mmol) in one portion. The reaction mixture was stirred for two days. Pyridine was evaporated and the residue was dissolved in EtOAc. The solution was washed with water (2×) followed by brine. The combined aqueous layer was re-extracted with EtOAc. This organic layer was washed with brine. The combined organic layer was then dried over anhydrous Na2SO4 and evaporated to get an oily residue which yielded white crystalline product from EtOAc and hexane. The mother liquor was chromatographed (400 g silica gel eluted with 20% EtOAc/hexane followed by 40% and finally 70%). The desired regioisomer, benzyl (1S,2R,4R)-4-hydroxy-2-(trityloxymethyl)cyclohexylcarbamate (33.08 g, 63.4 mmol, 86% yield) was obtained as a white solid. MS found [M−H]−=520.2 (AP/CI). 1H-NMR (400 MHz, CDCl3) δ, ppm 7.4 (d, J=7.12 Hz, 6H), 7.19-7.34 (m, 15H), 5.25-5.31 (m, 1H), 4.98-5.09 (m, 2H), 3.92 (s, 1H), 3.66 (bs, 1H), 3.14-3.24 (m, 1H), 2.97 (dd, J=9.41, 4.83 Hz, 1H), 1.98-2.08 (m, 1H), 1.91 (d, J=11.9 Hz, 2H), 1.76-1.84 (m, 1H), 1.36-1.49 (m, 2H), 1.39-1.43 (m, 1H), 1.19-1.30 (m, 1H). A small amount of the undesired isomer, benzyl (1S,2R,4R)-2-(hydroxymethyl)-4-(trityloxy)cyclohexyl carbamate (1.17 g, 2.243 mmol, 3.06% yield) was also obtained. MS found [M−H]−=520.2 (AP/CI). 1H-NMR (400 MHz, CDCl3) δ, ppm 7.48 (d, J=7.12 Hz, 6H), 7.32-7.40 (m, 5H), 7.21-7.32 (m, 10H), 5.05-5.14 (m, 2H), 4.96 (d, J=8.65 Hz, 1H), 3.89 (dd, J=8.39, 2.8 Hz, 1H), 3.84 (dd, J=10.7, 4.58 Hz, 1H), 3.46 (ddd, J=14.5, 9.92, 4.07 Hz, 1H), 3.07 (ddd, J=15.26, 10.43, 4.3 Hz, 1H), 1.66 (dd, J=14.24, 3.05 Hz), 1.43-1.51 (m, 1H), 1.30-1.40 (m, 2H), 1.14-1.23 (m, 1H), 0.79-0.91 (m, 1H), 0.72-0.79 (m, 1H).
