(2S,3S)-1,2-Epoxy-3-(Cbz-amino)-4-phenylbutane → benzyl (2S,3R)-4-((1S,3R)-3-(allyloxy)-6-methoxy-2,3-dihydro-1H-inden-1-ylamino)-3-hydroxy-1-phenylbutan-2-ylcarbamate

Participants

Reaction Conditions

Reaction Steps

Step V (1): Lithium perchlorate (838 mg, 7.88 mmol) was added to a solution of (1S,3R)-3-(allyloxy)-6-methoxy-2,3-dihydro-1H-inden-1-amine (765 mg, 3.49 mmol, from Step U(2)) and benzyl (S)-1-((S)-oxiran-2-yl)-2-phenylethyl-carbamate (1.04 g, 3.49 mmol) in CH3CN (50 mL). The reaction mixture was stirred at 50° C. for 36 h. The reaction mixture was poured into brine/NaHCO3 solution. Extracted with EtOAc, washed combined extracts with brine, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by silica gel chromatography (1-10% MeOH (with 0.1% triethylamine)/chloroform, linear gradient) to give 700 mg (39% yield) of benzyl (2S,3R)-4-((1S,3R)-3-(allyloxy)-6-methoxy-2,3-dihydro-1H-inden-1-ylamino)-3-hydroxy-1-phenylbutan-2-ylcarbamate. LC-MS (M+H)+=517.06; HRMS (M+H)+=517.2700; [α]D +14.45 (c=6.50 mg/mL, dichloroethane); 1H NMR (500 MHz, CDCl3) δ ppm 1.59 (s, 3H) 1.82-1.93 (m, 1H) 2.58-2.75 (m, 2H) 2.80-2.93 (m, 2H) 2.97-3.07 (m, 1H) 3.44-3.54 (m, 1H) 3.78 (s, 3H) 3.88 (t, 1H) 4.09 (t, J=5.19 Hz, 2H) 4.76 (s, 1H) 4.84-4.94 (m, 1H) 5.02 (s, 2H) 5.18 (d, J=10.38 Hz, 1H) 5.31 (dd, J=17.24, 1.37 Hz, 1H) 5.89-6.01 (m, 1H) 6.79-6.92 (m, 2H) 7.14-7.37 (m, 11H).

Provenance & Evidence