Dimethylformamide → 1,1-Bis(propan-2-yl) 3,3-dimethoxycyclobutane-1,1-dicarboxylate

HRID 2355445Notes

Reaction equation

HRID 2355445 reaction equation
[H-].[Na+].CN(C=O)C.[C:8]([O:17][CH:18]([CH3:20])[CH3:19])(=[O:16])[CH2:9][C:10]([O:12][CH:13]([CH3:15])[CH3:14])=[O:11].Br[CH2:22][C:23]([O:28][CH3:29])([O:26][CH3:27])[CH2:24]Br>O>[CH:18]([O:17][C:8]([C:9]1([C:10]([O:12][CH:13]([CH3:14])[CH3:15])=[O:11])[CH2:24][C:23]([O:28][CH3:29])([O:26][CH3:27])[CH2:22]1)=[O:16])([CH3:20])[CH3:19]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 83223Diisopropyl malonateHCID 27341961,3-Dibromo-2,2-dimethoxypropane

Product 1

HCID 49133591,1-Bis(propan-2-yl) 3,3-dimethoxycyclobutane-1,1-dicarboxylate

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
145 °C

Procedure

Following the procedure of Pigou and Scheisser (J. Org. Chem. 1988, 53, 3841), a 500 mL, 3-neck flask, fitted with a reflux condenser and thermocouple, was charged with NaH (60% in mineral oil, 4 g, 0.210 mol). DMF (100 mL) was added via syringe and the slurry was stirred under N2. Diisopropyl malonate was added at a rate so that the internal temperature did not rise above 70° C. After the H2 evolution had ceased, the flask was briefly opened and 1,3-dibromo-2,2-dimethoxypropane was added. The bath temperature was raised to 145° C. The reaction mixture was maintained at this temperature for 48 h. After this time the dark brown mixture was allowed to cool to rt. Water (50 mL) was added and the solvents were removed in vacuo. The residue was partitioned between ether (200 mL) and sat'd aq NH4Cl (200 mL) and the mixture filtered through a pad of Celite to remove solid impurities. The aqueous layer was extracted with ether (2×100 mL). The combined ether extracts were washed with brine, dried over Na2SO4, filtered and evaporated. Flash chromatography (SiO2, O-25% EtOAc in hexanes) gave semi-pure diisopropyl-3,3-dimethoxycyclobutane-1,1-dicarboxylate (28.5 g), which was used in the next step.

Workup

  1. customa 500 mL, 3-neck flask, fitted with a reflux condenser
  2. customdid not rise above 70° C
  3. temperatureThe reaction mixture was maintained at this temperature for 48 h
  4. temperatureto cool to rt
  5. customthe solvents were removed in vacuo
  6. customThe residue was partitioned between ether (200 mL)
  7. filtrationthe mixture filtered through a pad of Celite
  8. customto remove solid impurities
  9. extractionThe aqueous layer was extracted with ether (2×100 mL)
  10. washThe combined ether extracts were washed with brine
  11. dry with materialdried over Na2SO4
  12. filtrationfiltered
  13. customevaporated

Sources & evidence

ORD record
ord-45b7df6f5072467b91885c975c44ccd1
Source dataset
uspto-grants-2010_07
Patent number
US07754737B2

Reaction notes

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