Lithium Hexamethyldisilazide → (R)-4-Benzyl-3-[(S)-2-(4-benzyloxy-2,6-dimethyl-benzyl)-pent-4-enoyl]-oxazolidin-2-one

HRID 1013808Notes

Reaction equation

HRID 1013808 reaction equation
[CH2:1]([C@@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:19])[CH2:15][CH2:16][CH:17]=[CH2:18])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[CH2:30]([O:37][C:38]1[CH:39]=[C:40]([CH3:47])[C:41]([CH2:45]Br)=[C:42]([CH3:44])[CH:43]=1)[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1>C1COCC1>[CH2:1]([C@@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:19])[C@H:15]([CH2:45][C:41]1[C:42]([CH3:44])=[CH:43][C:38]([O:37][CH2:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)=[CH:39][C:40]=1[CH3:47])[CH2:16][CH:17]=[CH2:18])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 10858190(R)-4-Benzyl-3-pent-4-enoyloxazolidin-2-oneHCID 114267005-(Benzyloxy)-2-(bromomethyl)-1,3-dimethylbenzene

Product 1

HCID 67316268(R)-4-Benzyl-3-[(S)-2-(4-benzyloxy-2,6-dimethyl-benzyl)-pent-4-enoyl]-oxazolidin-2-oneYield 78%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

Cool a solution of (R)-4-Benzyl-3-pent-4-enoyl-oxazolidin-2-one (4.8 g, 19 mmol) in THF (100 mL) to −78° C. Treat the solution dropwise with 10M LiHMDS in THF (20 mL, 20 mmol) and stir at −78° C. for 30 minutes. Treat the solution with 5-Benzyloxy-2-bromomethyl-1,3-dimethyl-benzene (6.8 g, 22 mmol) and allow to slowly warm to room temperature. The reaction stirs 3 hr at room temperature. Quench the reaction with 1N HCl (aqueous) and extract with Et2O. Wash the organic with brine, dry over MgSO4, filter, and remove the solvent. Purify the crude by silica gel column chromatography using Hexanes:EtOAc to elute the pure product. Remove the solvent to afford 7.0 g (78%) of desired product. MS (m/e): 484 (M+1).

Workup

  1. temperatureto slowly warm to room temperature
  2. waitThe reaction stirs 3 hr at room temperature
  3. customQuench
  4. customthe reaction with 1N HCl (aqueous)
  5. extractionextract with Et2O
  6. washWash the organic with brine
  7. dry with materialdry over MgSO4
  8. filtrationfilter
  9. customremove the solvent
  10. customPurify the crude by silica gel column chromatography
  11. washEtOAc to elute the pure product
  12. customRemove the solvent

Sources & evidence

ORD record
ord-4656415709bf4fbd8467643569951843
Source dataset
uspto-grants-2011_07
Patent number
US07981918B2

Reaction notes

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