Lithium Hexamethyldisilazide → (R)-4-Benzyl-3-[(S)-2-(4-fluoro-3,5-dimethyl-benzyl)-pent-4-enoyl]-oxazolidin-2-one

HRID 1158144Notes

Reaction equation

HRID 1158144 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.[CH3:30][C:31]1[CH:32]=[C:33]([CH:36]=[C:37]([CH3:40])[C:38]=1[F:39])[CH2:34]Br>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]([CH2:34][C:33]1[CH:36]=[C:37]([CH3:40])[C:38]([F:39])=[C:31]([CH3:30])[CH:32]=1)[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 177507135-(Bromomethyl)-2-fluoro-1,3-dimethylbenzene

Product 1

HCID 59512579(R)-4-Benzyl-3-[(S)-2-(4-fluoro-3,5-dimethyl-benzyl)-pent-4-enoyl]-oxazolidin-2-oneYield 56%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a cooled (−78° C.) solution of (R)-4-benzyl-3-pent-4-enoyl-oxazolidin-2-one (0.500 g, 1.928 mmol) in 15 mL of THF, was added LiHMDS (2.9 mL, 2.9 mmol, 1.0 M in THF). The resulting mixture was stirred at −78° C. under N2 for 1 h and then a solution of 3,5-dimethyl-4-fluorobenzyl bromide (0.460 g, 2.121 mmol) in 5 mL of THF was added. After being stirred at −78° C. for 1 h followed by warming to room temperature over 2 h, the reaction mixture was quenched with 50 mL of aqueous NH4Cl solution and extracted with dichloromethane (50 mL×3). The combined organic extracts were dried, filtered, and concentrated under reduced pressure. The product was isolated by Flash column chromatography (silica gel) eluting with 0-100% dichloromethane/hexanes to give the title compound as colorless oil (0.221 g, 56% yield). GC-MS: tR=7.0 min; m/z 395 (M+).

Workup

  1. stirringAfter being stirred at −78° C. for 1 h
  2. temperatureby warming to room temperature over 2 h
  3. customthe reaction mixture was quenched with 50 mL of aqueous NH4Cl solution
  4. extractionextracted with dichloromethane (50 mL×3)
  5. customThe combined organic extracts were dried
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe product was isolated by Flash column chromatography (silica gel)
  9. washeluting with 0-100% dichloromethane/hexanes

Sources & evidence

ORD record
ord-e374d9c1f1b948b4bacc7b9161c694f1
Source dataset
uspto-grants-2010_10
Patent number
US07807720B2

Reaction notes

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