HCID 23519680, compound → HCID 59066510, compound

HRID 1837982Notes

Reaction equation

HRID 1837982 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C@@H:9]([C:15]([N:17]2[C@@H:21]([CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[CH2:20][O:19][C:18]2=[O:29])=[O:16])[N:10]([CH3:14])[C:11](=[O:13])[CH:12]=1>[Pd].CCO>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C@@H:8]1[CH2:12][C:11](=[O:13])[N:10]([CH3:14])[C@@H:9]1[C:15]([N:17]1[C@@H:21]([CH2:22][C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH2:20][O:19][C:18]1=[O:29])=[O:16]

Participants

4

Reactant 1

HCID 23519680HCID 23519680, compound

Product 1

HCID 59066510HCID 59066510, compoundYield 33.6%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalyst2×HCID 702EthanolSolvent3×

Procedure

To a slurry of 20% palladium on carbon (10 g, 0.06 equiv) in EtOH (1 L) was added a solution of diastereomeric mixture of 3-{[(2R)-3-(2-fluorophenyl)-1-methyl-5-oxo(3-pyrrolin-2-yl)carbonyl(4S)-4-benzyl-1,3-oxazolidin-2-one and (4S)-3-{[(2S)-3-(2-fluorophenyl)-1-methyl-5-oxo(3-pyrrolin-2-yl)]carbonyl}-4-benzyl-1,3-oxazolidin-2-one (154 g, 0.36 mol) in EtOH (1 L) and the resulting mixture was vigorously stirred under a H2 atmosphere (1 Atm) for 17 h. The reaction mixture was filtered through a pad of Celite®. NMR analysis of the filtrate showed only partial reduction, and the reaction mixture was treated with 10% palladium on carbon (Degussa type, 30 g, 0.1 equiv) in EtOH (4 L). After stirring under a H2 atmosphere (1 Atm) for 17 h, the reaction mixture was filtered through a pad of Celite®. The filtrate was concentrated under reduced pressure onto silica gel (250 g), then filtered through a plug of silica gel eluting with EtOAc. The filtrate was concentrated under reduced pressure onto silica gel (400 g) and purified by flash chromatography (2.5 kg silica gel, gradient from 25% to 60% EtOAc/hex) to afford (4S)-3-{[(2S,3S)-3-(2-fluorophenyl)-1-methyl-5-oxopyrrolidin-2-yl]carbonyl}-4-benzyl-1,3-oxazolidin-2-one (48 g, 30%) as a yellow solid: TLC (50% EtOAc/hex) Rf 0.22; 1H NMR (CDCl3; rotomeric mixture) δ 2.63 (dd, J=4.9, 9.5 Hz, 1H), 2.74-2.85 (m, 4H), 3.07 (dd, J=3.4, 13.2 Hz, 1H), 3.34 (t, J=8.3 Hz, 1H), 3.84-4.09 (m, 3H), 4.27 (dd, J=9.6, 18.8 Hz, 1H), 5.77 (d, J=8.8 Hz, 1H), 6.95-7.26 (m, 10H); HPLC ESMS m/z (rel abundance) 397 (MH+, 75%); and 3-{[(2R,3R)-3-(2-fluorophenyl)-1-methyl-5-oxopyrrolidin-2-yl]carbonyl}(4S)-4-benzyl-1,3-oxazolidin-2-one (48 g, 30%) as a yellow solid: TLC (50% EtOAc/hex) Rf 0.13; 1H NMR (CDCl3; rotomeric mixture) δ 1.63 (dd, J=11.2, 13.4 Hz, 1H), 2.64 (dd, J=2.8, 13.1 Hz, 1H), 2.75-2.93 (m, 5H), 3.95 (dd, J=3.4, 9.2 Hz, 1H), 4.09 (t, J=7.8 Hz, 1H), 4.40-4.50 (m, 2H), 5.77 (d, J=8.6 Hz, 1H), 7.04-7.12 (m, 4H), 7.21-7.32 (m, 5H); HPLC ES-MS m/z (rel abundance) 397 (MH+, 90%); and a mixture of the two diastereomers (17 g, 11%).

Workup

  1. filtrationThe reaction mixture was filtered through a pad of Celite®
  2. stirringAfter stirring under a H2 atmosphere (1 Atm) for 17 h
  3. filtrationthe reaction mixture was filtered through a pad of Celite®
  4. concentrationThe filtrate was concentrated under reduced pressure onto silica gel (250 g)
  5. filtrationfiltered through a plug of silica gel eluting with EtOAc
  6. concentrationThe filtrate was concentrated under reduced pressure onto silica gel (400 g)
  7. custompurified by flash chromatography (2.5 kg silica gel, gradient from 25% to 60% EtOAc/hex)

Sources & evidence

ORD record
ord-d490383178f4428d832e0c948a8bf3e6
Source dataset
uspto-grants-2004_08
Patent number
US06784167B2

Reaction notes

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