Ethyl Acetate → Dibenzyl 3(RS)-tert-butoxycarbonyl-2(R)-isobutylsuccinate

HRID 1857597Notes

Reaction equation

HRID 1857597 reaction equation
[C:1]([O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)(=[O:10])[CH2:2][C:3]([O:5][C:6]([CH3:9])([CH3:8])[CH3:7])=[O:4].[CH3:19][C:20]([CH3:23])([O-])[CH3:21].[K+].[CH3:25][CH2:26][O:27][C:28]([CH3:30])=[O:29]>CN(C=O)C>[C:6]([O:5][C:3]([CH:2]([C:1]([O:11][CH2:12][C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1)=[O:10])[C@@H:30]([CH2:19][CH:20]([CH3:23])[CH3:21])[C:28]([O:27][CH2:26][C:25]1[CH:17]=[CH:18][CH:13]=[CH:14][CH:15]=1)=[O:29])=[O:4])([CH3:9])([CH3:8])[CH3:7]

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 2736712Benzyl tert-butyl malonateHCID 23665647Potassium tert-butoxide

Product 1

HCID 18660804Dibenzyl 3(RS)-tert-butoxycarbonyl-2(R)-isobutylsuccinateYield 89%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

Benzyl tert-butyl malonate (24.9 g, 99.6 mmol) was dissolved in DMF (60 ml) and added portion wise with potassium tert-butoxide (13.4 g, 120 mmol) at 0° C. under stirring. The mixture was stirred at room temperature for 1 hour, then cooled to 0° C., and dropped in 1 hour with the solution of the Example 3-a compound (28.4 g, 99.6 mmol) dissolved in DMF (60 ml). After the reaction mixture was stirred at 5° C. overnight, it was added with AcOEt (2 l) and washed with a saturated aqueous solution of NaCl, 1N-HCl, a saturated aqueous solution of NaHCO3 and then the saturated aqueous solution of NaCl two times respectively. The organic layer was dried over anhydrous MgSO4, evaporated under reduced pressure and purified by column chromatography (silica gel; 750 g, elution with the mixed solvent; n-hexane: AcOEt=20:1), giving the title compound (40.0 g, 89%) of a colorless oil.

Workup

  1. stirringThe mixture was stirred at room temperature for 1 hour
  2. stirringAfter the reaction mixture was stirred at 5° C. overnight
  3. washwashed with a saturated aqueous solution of NaCl, 1N-HCl
  4. dry with materialThe organic layer was dried over anhydrous MgSO4
  5. customevaporated under reduced pressure
  6. custompurified by column chromatography (silica gel
  7. wash750 g, elution with the mixed solvent

Sources & evidence

ORD record
ord-14ca95b5eca140d4a62734f5567149e1
Source dataset
uspto-grants-2000_11
Patent number
US06147114

Reaction notes

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