Reaction Steps
3-[(2S)-2-Azido-2-(4-{[(triisopropylsilyl)oxy]methyl}cyclohexyl)-ethanoyl]-1,3-thiazolidine (isomer II, 130 mg, 0.29 mmol) from Example 6, Step I was dissolved in 3 mL of 15% HF (45% in H2O) in acetonitrile and stirred for 2 h. The solvent was removed and the residue was dissolved in ethyl acetate and then neutralized with aqueous sodium bicarbonate. The organics were separated, dried (Na2SO4) and filtered. Evaporation of the solvent afforded 78 mg of {4-[(1S)-1-azido-2-oxo-2-(1,3-thiazolidin-3-yl)ethyl]cyclohexyl}methanol. A portion of this material (24 mg, 0.084 mmol) was dissolved in wet THF and triphenyl phosphine (26 mg, 0.1 mmol) was added to the solution. The mixture was heated in an oil bath at 60° C. for 5 h, cooled, concentrated and purified by preparative TLC on silica gel (eluent: 5 to 10% methanol in CH2Cl2) to give the title compound. 1H NMR (500 MHz, CD3OD, HCl salt) δ 4.71 (dd, 1H, J=3 and 6 Hz), 4.58 (d, 0.45H, J=9.2 Hz), 4.48 (d, 0.55H, J=9.2 Hz), 4.18 (d, 0.45H, J=5.9 Hz), 4.11 (d, 0.55H, J=5.9 Hz), 3.93 (m, 0.55H), 3.88 (m, 0.45H), 3.88 (m, 0.45H), 3.79 (m, 1H), 3.17 (m, 1H), 3.36 (d, 2H, J=6.1 Hz), 3.09 (m, 1H), 1.98–1.78 (m, 4H), 1.40 (m, 1H), 1.26 (m, 1H), 1.11(m, 1H), 1.01 (m, 2H). 3-[(2S)-2-Azido-2-(4-{[(triisopropylsilyl)oxy]methyl}cyclohexyl)-ethanoyl]-1,3-thiazolidine (isomer I, 78 mg) was converted to the title compound in a manner identical to that described for isomer II. 1H NMR (500 MHz, CD3OD, HCl salt) δ 4.71 (dd, 1H, J=8 and 10 Hz), 4.58 (dd, 0.45H, J=2 and 9 Hz), 4.48 (d, 0.55H, J=2 and 9 Hz), 4.20 (d, 0.45H, J=6.2 Hz), 4.12 (d, 0.55H, J=6.2 Hz), 3.96 (m, 0.55H), 3.88 (m, 0.45H), 3.88 (m, 0.45H), 3.79 (m, 1H), 3.55 (d, 2H, J=5.9 Hz), 3.14 (m, 1H), 3.09 (m, 1H), 1.98 (m, 1H), 1.80 (m, 3H), 1.58 (m, 3H), 1.39 (m, 2H).
