Trifluoroacetic acid → 3-(1-Benzyl4-(s)-phenylpyrrolidine-3-(r)-carbonyl)-4(s)-benzyl oxazolidin-2-one

참여 물질

반응 단계

A solution of 402 g (1.3 mol) of 3-((E)-cinnamoyl)-4-(S)-benzyloxazolidin-2-one (from EXAMPLE 1, Step A) and 474 g (2.0 mol) of N-methoxymethyl-N-trimethylsilylmethyl benzyl amine in 4 L of CH2Cl2 at −10° C. was treated with 6 mL of TFA. The resulting mixture was stirred cold for 4 h and then was treated with an additional 4 mL of TFA. The reaction mixture was warmed to rt and stirred for 20 h. The reaction was quenched with 2 L of sat'd NaHCO3 and the layers were separated. The organic layer was washed with 1 L of sat'd NaCl and concentrated. Chromatography on 10 kg of silica gel using 4:1 v/v hexanes/EtOAc (24 L), then 7:3 v/v hexanes/EtOAc (36 L), then 3:2 v/v hexanes/EtOAc (32 L) afforded 260.9 g (45%) of 3-(1-benzyl-4-(S)-phenylpyrrolidine-3-(R)-carbonyl)-4-(S)-benzyloxazolidin-2-one and 247.5 g (43%) of 3-(1-benzyl-4-(R)-phenylpyrrolidine-3-(S)-carbonyl)-4-(S)-benzyloxazolidin-2-one. For 3-(1-benzyl-4-(S)-phenylpyrrolidine-3-(R)-carbonyl)-4-(S)-benzyloxazolidin-2-one: 1H NMR (500 MHz) δ 2.66 (t, J=8.0, 11H), 2.78 (dd, J=13.0, 9.0, 11H), 2.87 (dd, J=9.0, 4.5, 1H), 3.21-3.27 (m, 2H), 3.64 (d, J=11.5, 1H), 3.77 (d, J=11.5, 1H), 4.104.15 (m, 2H), 4.61-4.65 (m, 1H), 7.16-7.38 (15H). For 3-(1-benzyl-4-(R)-phenylpyrrolidine-3-(S)-carbonyl)-4-(S)benzyloxazolidin-2-one: 1H NMR (500 MHz) δ 2.69-2.76 (m, 2H), 2.82 (dd, J=9.5, 5.5, 1H), 3.14-3.22 (3H), 3.64 (d, J=13.0, 1H), 3.74 (d, J=13.0, 1H), 4.074.12 (m, 2H), 4.16 (t, J=9.0, 1H), 4.26-4.30 (m, 1H), 4.654.69 (m, 1H), 7.03-7.40 (15H).

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