Bromide ion → (1S,2S)-1-((2R,4R)-4-(allyloxy)-1-benzhydrylpyrrolidin-2-yl)-2-amino-3-(3,5-difluorophenyl)propan-1-ol

HRID 20935Notes

Reaction equation

HRID 20935 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:34]=[C:35]([F:37])[CH:36]=1)[CH2:5][C@H:6]1[C@@H:10]([C@H:11]2[CH2:15][C@@H:14]([O:16][CH2:17][CH:18]=[CH2:19])[CH2:13][N:12]2[CH:20]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[O:9]C(=O)[NH:7]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>[CH2:17]([O:16][C@H:14]1[CH2:13][N:12]([CH:20]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C@@H:11]([C@@H:10]([OH:9])[C@@H:6]([NH2:7])[CH2:5][C:4]2[CH:34]=[C:35]([F:37])[CH:36]=[C:2]([F:1])[CH:3]=2)[CH2:15]1)[CH:18]=[CH2:19]

Participants

6

Reactant 4

HCID 259Bromide ionHCID 11430Potassium CarbonateHCID 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 59346850(1S,2S)-1-((2R,4R)-4-(allyloxy)-1-benzhydrylpyrrolidin-2-yl)-2-amino-3-(3,5-difluorophenyl)propan-1-olYield 87%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Step C (9): (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-fe0646da00fa43a28ac7329b6c131d74
Source dataset
uspto-grants-2010_06
Patent number
US07745470B2

Reaction notes

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