Lithium Hexamethyldisilazide → (4R,5S)-3-((R)-3-cyclopentyl-2-phenyl-propionyl)-4-methyl-5-phenyl-oxazolidin-2-one

HRID 889592Notes

Reaction equation

HRID 889592 reaction equation
[CH3:1][C@@H:2]1[C@H:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[O:5][C:4](=[O:13])[N:3]1[C:14](=[O:22])[CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH:33]1([CH2:38]OS(C(F)(F)F)(=O)=O)[CH2:37][CH2:36][CH2:35][CH2:34]1>C1COCC1.C(OCC)(=O)C>[CH:33]1([CH2:38][C@H:15]([C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)[C:14]([N:3]2[C@H:2]([CH3:1])[C@H:6]([C:7]3[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=3)[O:5][C:4]2=[O:13])=[O:22])[CH2:37][CH2:36][CH2:35][CH2:34]1

Participants

6

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 11748453(4R,5S)-4-methyl-5-phenyl-3-phenylacetyl-oxazolidin-2-oneHCID 57617550Trifluoromethanesulfonic acid cyclopentylmethyl ester

Product 1

HCID 67024850(4R,5S)-3-((R)-3-cyclopentyl-2-phenyl-propionyl)-4-methyl-5-phenyl-oxazolidin-2-one

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

The title A compound, (4R,5S)-4-methyl-5-phenyl-3-phenylacetyl-oxazolidin-2-one (5.00 g, 16.93 mmol) is dissolved in anhydrous THF (50 mL) and cooled to −78° C. Lithium bis(trimethylsilyl)amide (1 M in THF, 16.93 mL, 16.93 mmol) is added dropwise over 10 min. To this is added a solution of the title B compound, trifluoromethanesulfonic acid cyclopentylmethyl ester (3.93 g, 16.93 mmol) in anhydrous THF (15 mL). The reaction is stirred at −78° C. for 10 min, then the cold bath is removed. The reaction is allowed to stir and warm to RT. After one hour, the reaction is concentrated to remove the solvent, resulting in a yellow oil. This is dissolved in ethyl acetate (300 mL) and washed with water (2×200 mL). The organic solution is dried over anhydrous sodium sulfate, filtered, and concentrated to a yellow oil. This is recrystallized from hexanes to afford (4R,5S)-3-((R)-3-cyclopentyl-2-phenyl-propionyl)-4-methyl-5-phenyl-oxazolidin-2-one as a white solid: 1H NMR (400 MHz, DMSO-D6) 0.8 (d, J=6.6 Hz, 3 H) 1.1 (d, J=16.2 Hz, 2 H) 1.4 (m, 2 H) 1.5 (d, J=5.8 Hz, 2 H) 1.6 (s, 2 H) 1.8 (d, J=7.1 Hz, 2 H) 2.0 (d, J=13.4 Hz, 1 H) 4.8 (s, 1 H) 5.1 (s, 1 H) 5.7 (d, J=7.1 Hz, 1 H) 7.3 (s, 1 H) 7.4 (m, 9 H); LC/MS 378.2 (M+1).

Workup

  1. customthe cold bath is removed
  2. stirringto stir
  3. temperaturewarm to RT
  4. waitAfter one hour
  5. concentrationthe reaction is concentrated
  6. customto remove the solvent
  7. customresulting in a yellow oil
  8. washwashed with water (2×200 mL)
  9. dry with materialThe organic solution is dried over anhydrous sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated to a yellow oil
  12. customThis is recrystallized from hexanes

Sources & evidence

ORD record
ord-f4e736d1ae5a4339ba9d1c32d297bc8d
Source dataset
uspto-grants-2012_08
Patent number
US08252931B2

Reaction notes

Loading…