Diisopropylamine → Di-tert-butyl 3-hydroxy-3-methylpentanedioate

HRID 358409Notes

Reaction equation

HRID 358409 reaction equation
[CH2:1]([Li])CCC.[O:6]1CC[CH2:8][CH2:7]1.C(N[CH:15]([CH3:17])[CH3:16])(C)C.[C:18]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])(=[O:20])[CH3:19].[C:26]([O:29]CC)(=[O:28])[CH3:27]>C1CCCCC1>[CH3:8][C:7]([OH:6])([CH2:27][C:26]([O:29][C:15]([CH3:16])([CH3:17])[CH3:1])=[O:28])[CH2:19][C:18]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20]

Participants

7

Reactant 5

HCID 7912DiisopropylamineHCID 8028TetrahydrofuranHCID 8857Ethyl AcetateHCID 10908tert-Butyl acetateHCID 178418339Butyllithium

Product 1

HCID 13267731Di-tert-butyl 3-hydroxy-3-methylpentanedioate

Reagents, catalysts & solvents 1

HCID 8078CyclohexaneSolvent

Conditions

Temperature
-40 °C

Procedure

187 g of a solution of 19.5% butyllithium in cyclohexane (36.4 g of butyllithium) were added over 5 minutes at -40° C. under argon to 500 ml of tetrahydrofuran and then 57.5 g of diisopropylamine were added over 5 minutes at -40° C. The mixture was stirred at -40° C. for 30 minutes and 66 g of tert.-butyl acetate were added thereto at -40° C. The mixture was stirred at -40° C. for 30 minutes and then 27.5 g (≃0.55 mole per mole of tert.-butyl acetate) of ethyl acetate were added at -40° C. over 30 minutes. The mixture was stirred at -40° C. for two hours and the temperature allowed to rise to 20° C. under reduced pressure. The mixture was evaporated to dryness under reduced pressure at 20° C. and the residue was taken up in 200 ml of methylene chloride. The solution was cooled to 0° C. and 100 ml of water were added. The decanted aqueous phase was extracted with methylene chloride and the combined organic phases were adjusted to a pH of 1 by addition of 22° Be hydrochloric acid. The organic phase was washed with water, dried and evaporated to dryness under reduced pressure to obtain a lightly colored liquid which was rectified at 1 mm Hg to obtain 25 g of ditert.-butyl 3-methyl-3-hydroxy-glutarate with a boiling point of 95°±` C. at1 mm Hg.

Workup

  1. customat -40° C
  2. stirringThe mixture was stirred at -40° C. for 30 minutes
  3. stirringThe mixture was stirred at -40° C. for two hours
  4. customto rise to 20° C. under reduced pressure
  5. customThe mixture was evaporated to dryness under reduced pressure at 20° C.
  6. temperatureThe solution was cooled to 0° C.
  7. addition100 ml of water were added
  8. extractionThe decanted aqueous phase was extracted with methylene chloride
  9. additionthe combined organic phases were adjusted to a pH of 1 by addition of 22° Be hydrochloric acid
  10. washThe organic phase was washed with water
  11. customdried
  12. customevaporated to dryness under reduced pressure
  13. customto obtain a lightly colored liquid which

Sources & evidence

ORD record
ord-85eda89cc0f248c9ba1cf304aa9e629a
Source dataset
uspto-grants-1984_08
Patent number
US04467108

Reaction notes

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