1,1'-Carbonyldiimidazole → (4s)-4-Benzyl-3-[(8-bromo-6-fluoro-2,3-dihydro-1h-pyrrolo[1,2-a]indol-1-yl)acetyl]-1,3-oxazolidin-2-one

HRID 857341Notes

Reaction equation

HRID 857341 reaction equation
[CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[NH:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([Li])CCC.[Br:19][C:20]1[C:21]2[CH:22]=[C:23]3[CH:32]([CH2:33][C:34](O)=[O:35])[CH2:31][CH2:30][N:24]3[C:25]=2[CH:26]=[C:27]([F:29])[CH:28]=1.C(N1C=CN=C1)(N1C=CN=C1)=O>C1COCC1>[CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:34](=[O:35])[CH2:33][CH:32]1[C:23]2=[CH:22][C:21]3[C:20]([Br:19])=[CH:28][C:27]([F:29])=[CH:26][C:25]=3[N:24]2[CH2:30][CH2:31]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 736225(S)-4-Benzyl-2-oxazolidinoneHCID 21867415(+/-)-(8-bromo-6-fluoro-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetic acidHCID 178418339Butyllithium

Product 1

HCID 58760766(4s)-4-Benzyl-3-[(8-bromo-6-fluoro-2,3-dihydro-1h-pyrrolo[1,2-a]indol-1-yl)acetyl]-1,3-oxazolidin-2-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution (S)-(−)-4-benzyl-2-oxazolidinone (7.8 g, 43.8 mmol) in THF (300 mL) at −78° C. was slowly added 1.6M n-butyllithium (27.3 mL, 43.8 mmol). The mixture was stirred for 30 minutes at −78° C. and a mixture of the compound of Step 1 (10.5 g, 33.7 mmol) and 1,1′-carbonyldiimidazole (6 g, 37 mmol) in THF (100 mL) was added. The mixture was stirred for 30 minutes at −78° C. and then warmed to −30° C. and stirred for 2 hours. The reaction was quenched with saturated NH4Cl, the phases were separated and the aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4 and concentrated. The residue was purified by silica gel chromatography eluted with 10% EtOAc in Toluene, which permitted the separation of the two diastereomers. Both isomers were obtained as an yellow solid with diastereomeric excess >95%.

Workup

  1. customat −78° C.
  2. additionwas added
  3. stirringThe mixture was stirred for 30 minutes at −78° C.
  4. temperaturewarmed to −30° C.
  5. stirringstirred for 2 hours
  6. customThe reaction was quenched with saturated NH4Cl
  7. customthe phases were separated
  8. extractionthe aqueous layer was extracted with EtOAc
  9. washThe combined organic layers were washed with brine
  10. dry with materialdried over Na2SO4
  11. concentrationconcentrated
  12. customThe residue was purified by silica gel chromatography
  13. washeluted with 10% EtOAc in Toluene, which
  14. customthe separation of the two diastereomers
  15. customBoth isomers were obtained as an yellow solid with diastereomeric excess >95%

Sources & evidence

ORD record
ord-d04a3438d65e41b3af5ca3ebce9c9050
Source dataset
uspto-grants-2006_12
Patent number
US07144913B2

Reaction notes

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