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

HRID 1386663Notes

Reaction equation

HRID 1386663 reaction equation
[C:1]([N:11]1[C@@H:15]([CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH2:14][O:13][C:12]1=[O:23])(=[O:10])/[CH:2]=[CH:3]/[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.CO[CH2:26][N:27]([CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[CH2:28][Si](C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH2:33]([N:27]1[CH2:28][C@H:3]([C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=2)[C@@H:2]([C:1]([N:11]2[C@@H:15]([CH2:16][C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=3)[CH2:14][O:13][C:12]2=[O:23])=[O:10])[CH2:26]1)[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.[CH2:33]([N:27]1[CH2:28][C@@H:3]([C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=2)[C@H:2]([C:1]([N:11]2[C@@H:15]([CH2:16][C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=3)[CH2:14][O:13][C:12]2=[O:23])=[O:10])[CH2:26]1)[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1

Participants

6

Reactant 3

HCID 6422Trifluoroacetic acid2×HCID 353442Benzyl(methoxymethyl)((trimethylsilyl)methyl)amineHCID 10470464(4S)-4-benzyl-3-[(2E)-3-phenylprop-2-enoyl]-1,3-oxazolidin-2-one

Product 2

HCID 213410683-(1-benzyl-4-(R)-phenylpyrrolidine-3-(S)-carbonyl)-4-(S)-benzyloxazolidin-2-oneYield 43%HCID 213410693-(1-Benzyl4-(s)-phenylpyrrolidine-3-(r)-carbonyl)-4(s)-benzyl oxazolidin-2-oneYield 45%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

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).

Workup

  1. stirringstirred for 20 h
  2. customThe reaction was quenched with 2 L of sat'd NaHCO3
  3. customthe layers were separated
  4. washThe organic layer was washed with 1 L of sat'd NaCl
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-de197eb260e44520afbf4da0d2c064af
Source dataset
uspto-grants-2001_07
Patent number
US06265434B1

Reaction notes

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