Toluene → Tert-butyl 3-cyclohexylmethyl-4-(4-isopropyl-2-oxooxazolidin-3-yl)-4-oxobutyrate

HRID 1060743Notes

Reaction equation

HRID 1060743 reaction equation
C[Si](C)(C)[N-][Si](C)(C)C.[Na+].C1(C)C=CC=CC=1.[CH:18]1([CH2:24][CH2:25][C:26]([N:28]2[C@@H:32]([CH:33]([CH3:35])[CH3:34])[CH2:31][O:30][C:29]2=[O:36])=[O:27])[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1.[C:37]([O:41][C:42](=[O:45])[CH2:43]Br)([CH3:40])([CH3:39])[CH3:38]>C1COCC1.Cl>[CH:18]1([CH2:24][CH:25]([C:26]([N:28]2[CH:32]([CH:33]([CH3:34])[CH3:35])[CH2:31][O:30][C:29]2=[O:36])=[O:27])[CH2:43][C:42]([O:41][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:45])[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23]1

Participants

7

Reactant 4

HCID 1140TolueneHCID 79177tert-Butyl bromoacetateHCID 2724254Sodium bis(trimethylsilyl)amideHCID 69156991(S)-3-cyclohexylpropionyl-4-isopropyloxazolidin-2-one

Product 1

HCID 18628724Tert-butyl 3-cyclohexylmethyl-4-(4-isopropyl-2-oxooxazolidin-3-yl)-4-oxobutyrateYield 61%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-10 °C

Procedure

A solution of sodium hexamethyldisilazide (92.4 mL of a 0.6M toluene solution, Aldrich) in THF (70 mL) was cooled to −78° C. and then treated with a solution of (S)-3-cyclohexylpropionyl-4-isopropyloxazolidin-2-one (10.5 g, 39.3 mmol) in THF (30 mL) added dropwise over 10 minutes. The mixture was stirred for 1 hour and then treated with a solution of tert-butylbromoacetate (9.75 mL, 50 mmol) in THF (20 mL) added dropwise. The mixture was stirred for 1 hour, while warming to −10° C. The mixture reaction was diluted with 1M hydrochloric acid (100 mL) and the dilution was extracted with ethyl acetate (200 mL). The extract was washed with saturated aqueous sodium bicarbonate (100 mL) and brine (100 mL), dried (MgSO4), filtered and concentrated to dryness. The residue was dissolved in hexane and product was crystallized out to provide tert-butyl 3-cyclohexylmethyl-4-(4-isopropyl-2-oxooxazolidin-3-yl)-4-oxobutyrate (9.09 g, 61%). MS (M+1): 382.

Workup

  1. additionadded dropwise over 10 minutes
  2. additionadded dropwise
  3. stirringThe mixture was stirred for 1 hour
  4. customThe mixture reaction
  5. extractionthe dilution was extracted with ethyl acetate (200 mL)
  6. washThe extract was washed with saturated aqueous sodium bicarbonate (100 mL) and brine (100 mL)
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated to dryness
  10. dissolutionThe residue was dissolved in hexane
  11. customproduct was crystallized out

Sources & evidence

ORD record
ord-09da4d66629e49eabacfb64ab6fe6c0a
Source dataset
uspto-grants-2003_02
Patent number
US06525036B2

Reaction notes

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