4-Methylmorpholine → 1-[trans-4-(n-Tert-butoxycarbonylglycylamino)-n-tert-butoxycarbonyl-l-prolyl]-4-(3,5-dichlorophenoxy)piperidine

Participants

Reaction Steps

N-Methylmorpholine (120 μL) and ]-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (188 mg) were added to a solution of trans-4-(N-tert-butoxycarbonylglycylamino)-N-tert-butoxycarbonyl-L-proline (Compound D103 (B), 400 mg), 4-(3,5-dichlorophenoxy)piperidine (518 mg), and 1-hydroxybenzotriazole (140 mg) in tetrahydrofuran (12 mL) and N,N-dimethylformamide (4 mL) at room temperature. After stirring at room temperature for 12 hr, the reaction mixture was partitioned between ethyl acetate and 1 N hydrochloric acid. The organic layer was washed with saturated sodium hydrogen carbonate and brine. After drying over anhydrous sodium sulfate, the organic layer was evaporated in vacuo. The residue was washed with hexane to give the titled compound (671 mg) as a white solid: 1H NMR (400 MHz, CDCl3) δ 1.43 (s, 9H), 1.46 (s, 9H), 1.70-2.00 (m, 4H), 2.14-2.29 (m, 2H), 3.35-3.82 (m, 8H), 4.51-4.60 (m, 2H), 4.64 (br t, 0.5H), 4.78 (m, 0.5H), 5.11 (br s, 1H), 6.40 (m, 1H), 6.77-6.80 (m, 2H), and 6.96-6.98 (m, 1H); IR (KBr) 3311, 2978, 1701, 1655, 1570, 1441, 1255, 1163, 1049 cm−1; mass spectrum (FAB+) m/e 615 (M).

Provenance & Evidence