Diisopropylamine → Ethyl methyl 2,2'-cyclopropane-1,1-diyldiacetate

HRID 626445Notes

Reaction equation

HRID 626445 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[C:13]([O:16][CH2:17][CH3:18])(=[O:15])[CH3:14].[C:19]1(=[CH:22][C:23]([O:25][CH3:26])=[O:24])[CH2:21][CH2:20]1.[Cl-].[NH4+]>CCCCCC.C1COCC1>[C:19]1([CH2:14][C:13]([O:16][CH2:17][CH3:18])=[O:15])([CH2:22][C:23]([O:25][CH3:26])=[O:24])[CH2:21][CH2:20]1

Participants

8

Reactant 5

HCID 7912DiisopropylamineHCID 8857Ethyl AcetateHCID 25517Ammonium ChlorideHCID 10964443Methyl 2-cyclopropylideneacetateHCID 178418339Butyllithium

Product 1

HCID 118106388Ethyl methyl 2,2'-cyclopropane-1,1-diyldiacetate

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 8058HexaneSolvent

Conditions

Temperature
-40 °C

Procedure

240 ml (1.70 mol) of diisopropylamine were dissolved in 700 ml of abs. THF, the mixture was cooled to −40° C. and 681 ml (1.7 mol) of a 2.5 M solution of n-butyllithium in hexane were added slowly. The solution was stirred at −40° C. for 30 min and then cooled to −78° C., and a solution of 166.6 ml (1.7 mol) of ethyl acetate p.a. in 200 ml of abs. THF was added. After the end of the addition, the mixture was stirred at −78° C. for another 30 min 159 g (crude product, about 1.42 mol) of methyl cyclopropylideneacetate, dissolved in a little abs. THF, were then added dropwise. The reaction mixture was stirred at −78° C. for 1 h and then, via −40° C., slowly warmed to about 0° C., and a saturated aqueous ammonium chloride solution was finally added. The mixture was extracted with ethyl acetate and the organic phase was washed with 1 N hydrochloric acid and sat. sodium chloride solution, dried over sodium sulphate and concentrated under reduced pressure. The residue was purified chromatographically on silica gel (mobile phase cyclohexane/ethyl acetate 9:1). This gave 109.5 g of the target compound which was contaminated by the diethyl ester derivative and was not purified any further.

Workup

  1. temperaturecooled to −78° C.
  2. additionAfter the end of the addition
  3. dissolutiondissolved in a little abs
  4. stirringThe reaction mixture was stirred at −78° C. for 1 h
  5. temperaturevia −40° C., slowly warmed to about 0° C.
  6. extractionThe mixture was extracted with ethyl acetate
  7. washthe organic phase was washed with 1 N hydrochloric acid and sat. sodium chloride solution
  8. dry with materialdried over sodium sulphate
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified chromatographically on silica gel (mobile phase cyclohexane/ethyl acetate 9:1)
  11. customwas not purified any further

Sources & evidence

ORD record
ord-8b950220eb2c4d6aa63dd1f1c155f6e8
Source dataset
uspto-grants-2016_04
Patent number
US09309198B2

Reaction notes

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