Bromide ion → (4S,5S)-4-(3,5-difluorobenzyl)-5-((2R,4R)-1-benzhydryl-4-hydroxypyrrolidin-2-yl)oxazolidin-2-one

HRID 132940Notes

Reaction equation

HRID 132940 reaction equation
C(OC(N1C[C@H](O)C[C@@H]1C(O)=O)=O)(C)(C)C.[F:17][C:18]1[CH:19]=[C:20]([CH:50]=[C:51]([F:53])[CH:52]=1)[CH2:21][C@H:22]1[C@@H:26]([C@H:27]2[CH2:31][C@@H:30]([O:32]CC=C)[CH2:29][N:28]2[CH:36]([C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[O:25][C:24](=[O:49])[NH:23]1.FC1C=C(C=C(F)C=1)C[C@H]1[C@@H]([C@H]2C[C@@H](OCC=C)CN2)OC(=O)N1.[Br-].C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[F:53][C:51]1[CH:50]=[C:20]([CH:19]=[C:18]([F:17])[CH:52]=1)[CH2:21][C@H:22]1[C@@H:26]([C@H:27]2[CH2:31][C@@H:30]([OH:32])[CH2:29][N:28]2[CH:36]([C:37]2[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=2)[C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[O:25][C:24](=[O:49])[NH:23]1

Participants

7

Reactant 5

HCID 259Bromide ionHCID 11430Potassium CarbonateHCID 688616N-Boc-cis-4-hydroxy-D-prolineHCID 67316078(4S,5S)-4-(3,5-difluorobenzyl)-5-((2R,4R)-4-(allyloxy)-1-benzhydrylpyrrolidin-2-yl)oxazolidin-2-oneHCID 67316146(4S,5R)-4-(3,5-difluorobenzyl)-5-((2R,4R)-4-(allyloxy)pyrrolidin-2-yl)oxazolidin-2-one

Product 1

HCID 58608196(4S,5S)-4-(3,5-difluorobenzyl)-5-((2R,4R)-1-benzhydryl-4-hydroxypyrrolidin-2-yl)oxazolidin-2-oneYield 87%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Step J (1): (4S,5S)-4-(3,5-difluorobenzyl)-5-((2R,4R)-4-(allyloxy)-1-benzhydrylpyrrolidin-2-yl)oxazolidin-2-one. A mixture of (4S,5R)-4-(3,5-difluorobenzyl)-5-((2R,4R)-4-(allyloxy)pyrrolidin-2-yl)oxazolidin-2-one (Step C (8), 2.03 g, 6.0 mmol), benzylhydryl bromide (2.22 g, 9.0 mmol), and potassium carbonate (1.24 g, 9.0 mmol) in acetonitrile (40 mL) was stirred at reflux for 35 min. After cooling to rt, the mixture was filtered and concentrated in vacuo. The crude mixture was purified by Flash Chromatography (silica gel, 0-7.5% methanol/chloroform) to give a slightly yellow oil as the title compound (2.64 g, 87% yield): 1H NMR (CDCl3, 300 MHz) δ 1.95-2.23 (2H, m), 2.36 (1H, t, J=12 Hz), 2.70 (1H, m), 3.02 (2H, d, J=6 Hz), 3.48 (1H, m), 3.71-3.99 (4H, m), 4.70 (1H, s), 4.78 (1H, t, J=6 Hz), 4.93 (1H, s), 5.12 (1H, m), 5.22 (1H, dd, J=3, 18 Hz), 5.84 (1H, m), 6.49 (1H, d, J=6 Hz), 6.67 (1H, m), 7.20-7.39 (11H, m).

Workup

  1. temperatureat reflux for 35 min
  2. filtrationthe mixture was filtered
  3. concentrationconcentrated in vacuo
  4. customThe crude mixture was purified by Flash Chromatography (silica gel, 0-7.5% methanol/chloroform)

Sources & evidence

ORD record
ord-0aa5d56f61494765b3b5f00dd2a9b740
Source dataset
uspto-grants-2008_06
Patent number
US07388007B2

Reaction notes

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