HCID 178447109, compound → HCID 178447110, compound

Participants

Reaction Steps

To a solution of (3R,4R,5S)-ethyl 5-((Z)-2,3-bis(tert-butoxycarbonyl)guanidino-4-(2,2-difluoroacetamido)-3-(pentan-3-yloxy)cyclohex-1-enecarboxylate 6b (250 mg) in dioxane (5 ml) 5% solution of lithium hydroxide (2.5 ml) was added and the reaction mixture was stirred at room temperature for 45 min. Then lithium hydroxide was passivated by adding acetic acid (300 mcl), the solvents were evaporated in vacuo. The solid was extracted with isopropyl alcohol, the extract was dried over Na2SO4 and evaporated in vacuo. It gives (3R,4R,5S)-5-((Z)-2,3-bis(tert-butoxycarbonyl)guanidino)-4-(2,2-difluoroacetamido)-3-(pentan-3-yloxy)cyclohex-1-enecarboxylic acid 8b (200 mg, 84%). LCMS (M+H): found 563; calculated 562.62. The obtained acid 8b (200 mg) was dissolved in 10% solution of trifluoroacetic acid in methylene chloride (2 ml) and stirred at room temperature for 12 h. Then the solvents were evaporated in vacuo. (3R,4R,5S)-4-(2,2-Difluoroacetamido)-5-guanidino-3-(pentan-3-yloxy)cyclohex-1-enecarboxylic acid 1.4 was separated by HPLC method. LCMS (M+H): found 363; calculated 362.28. 1H NMR (DMSO-d6), 400 MHz: 8.68 (d, J=8.4 Hz, 1H), 7.6 (d, J=10 Hz, 1H), 7.26 (br, 2H), 6.91 (br, 2H), 6.63 (s, 1H), 6.27 (t, J=53.6 Hz, 1H), 4.18 (d, J=8 Hz, 2H), 4.09 (m, 1H), 3.54 (q, J=10 Hz, 1H), 3.39 (m, 2H), 2.57 (dd, J1=18 Hz, J2=6 Hz, 1H), 2.31 (m, 1H), 1.44 (m, 4H), 0.85 (t, J=8 Hz, 3H), 0.795(t, J=7.6 Hz, 3H).

Provenance & Evidence