1,1'-Carbonyldiimidazole → HCID 86629528, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of methoxyamine HCl (0.25 g, 3.04 mmol) in CH3CN (5 ml) was added CDI (0.49 g, 3.04 mmol) and DIPEA (0.53 mL, 3.04 mmol). The mixture was stirred at 60° C. for 2 h, then a solution of {(R)-3-[4-(3-chloro-benzylamino)-piperidin-1-yl]-butyl}-carbamic acid tert-butyl ester (305 mg, 0.76 mmol) in CH3CN (5 ml) was added to the previous mixture. After stirring at 60° C. overnight, the mixture was concentrated in vacuo and diluted with CH2Cl2 (15 ml) and saturated NaHCO3 (20 ml). The aqueous layer was extracted with CH2Cl2 (3×10 ml), then the combined organic extracts were dried over Na2SO4 and concentrated. The crude product contained 2:1 product/starting material in the 1H NMR and was purified by flash chromatography (CH2Cl2, 7% MeOH, 1% NH4OH) to afford ((R)-3-{4-[1-(3-chloro-benzyl)-3-methoxy-ureido]-piperidin-1-yl}-butyl)-carbamic acid tert-butyl ester as a yellow oil (215 mg, 60%). 1H NMR (CDCl3) δ 0.92-0.95 (d, 3H, J=9 Hz), 1.37 (s, 9H), 1.47-1.82 (m, 6H), 2.13-2.25 (m, 1H), 2.48-2.57 (m, 1H), 2.63-2.89 (m, 3H), 2.99-3.09 (m, 1H), 3.23-3.38 (m, 1H), 3.65 (s, 3H), 4.14-4.26 (m, 1H), 4.31 (s, 2H), 5.90 (br s, 1H), 6.97 (s, 1H), 7.06-7.17 (m, 1H), 7.22 (s, 1H), 7.29 (s, 1H), 7.69 (s, 1H).

Provenance & Evidence