Reaction Steps
To a solution of ethyl 2-(4-(3-(2-(tert-butoxycarbonylamino)cyclohexyl)ureido)-2-chlorophenyl)acetate (452 mg, 0.996 mmol) in a mixture of THF:EtOH (1:2, 12 mL) at room temperature, was added NaBH4 (124 mg, 3.29 mmol) and LiCl (139 mg, 3.29 mmol). The reaction mixture was stirred overnite. The solvents were distilled off and the crude was diluted with saturated aqueous NH4Cl (20 mL), the product was extracted with ethyl acetate (2×20 mL). The combined organic extracts were dried over Na2SO4 and the solvent distilled off under reduced pressure. The crude product was purified by flash column chromatography to separate cis 964 mg, 0.155 mmol) and trans (83 mg, 0.201 mmol) diastereomers. These alcohols were converted into tosylates using general procedure for the preparation of tosylates. 1H NMR (cis): 1.23-1.26 (m, 3H), 1.36 (s, 9H), 1.70-1.74 (m, 2H), 1.99-2.06 (m, 2H), 2.41-2.43 (m, 1H), 2.92 (t, 2H, J=6.4 Hz), 3.25-3.29 (m, 1H), 3.51-3.54 (m, 1H), 3.83-3.86 (m, 2H), 5.03 (d, 1H, J=8.8 Hz), 5.62 (d, 1H, J=8.4 Hz), 7.04 (d, 1H, J=8.4 Hz), 7.09 (d, 1H, J=8 Hz), 7.32 (s, 2H). 1H NMR (trans): 1.26-1.29 (m, 1H), 1.37-1.42 (m, 12H), 1.69-1.72 (m, 2H), 1.97 (s, 1H), 2.53-2.55 (m, 1H), 2.85 (t, 2H, J=6.4 Hz), 3.75-3.77 (m, 3H), 3.97-3.99 (m, 1H), 5.15 (br s, 1H), 5.86 (br s, 1H), 6.98-7.05 (m, 2H), 7.30 (s, 1H), 7.41 (s, 2H).
