Sodium hydride → Diallyl 2-(4-cyanobutyl)malonate

HRID 1672677Notes

Reaction equation

HRID 1672677 reaction equation
[H-].[Na+].[C:3]([O:12][CH2:13][CH:14]=[CH2:15])(=[O:11])[CH2:4][C:5]([O:7][CH2:8][CH:9]=[CH2:10])=[O:6].Br[CH2:17][CH2:18][CH2:19][CH2:20][C:21]#[N:22].[Cl-].[NH4+]>O1CCOCC1>[C:21]([CH2:20][CH2:19][CH2:18][CH2:17][CH:4]([C:5]([O:7][CH2:8][CH:9]=[CH2:10])=[O:6])[C:3]([O:12][CH2:13][CH:14]=[CH2:15])=[O:11])#[N:22]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 794355-BromopentanenitrileHCID 228227Diallyl malonate

Product 1

HCID 57831342Diallyl 2-(4-cyanobutyl)malonateYield 43%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
40 °C

Procedure

21.71 g (542.9 mmol; 60% pure) of sodium hydride are added in portions to a solution of 100 g (542.9 mmol) of diallyl malonate in 700 ml of dry dioxane at 0° C. After gas evolution ceases, the reaction mixture is warmed to 40° C. and stirred for 1 hour. Then 43.98 g (271.5 mmol) of 5-bromovaleronitrile in 350 ml of dry dioxane are added dropwise, and the mixture is stirred at 110° C. for 12 hours. After the reaction is complete, the mixture is cooled to room temperature, mixed with 400 ml of saturated ammonium chloride solution and extracted with ethyl acetate. After phase separation, the aqueous phase is back-extracted three times with 250 ml of ethyl acetate each time. After the organic phases have been combined they are washed with saturated sodium chloride solution and dried over sodium sulfate, and then the solvent is stripped off in vacuo. Excess diallyl malonate is subsequently removed by high vacuum distillation (boiling point: 57° C.; 0.074 mbar). The distillation residue is purified by flash chromatography on silica gel (mobile phase: cyclohexane/ethyl acetate 2:1). 105 g (233 mmol, approx. 60% purity, 43% yield) of a liquid are obtained. This product is reacted without further purification in the subsequent stage. A small amount is purified by preparative HPLC for analytical characterization.

Workup

  1. stirringthe mixture is stirred at 110° C. for 12 hours
  2. temperaturethe mixture is cooled to room temperature
  3. extractionextracted with ethyl acetate
  4. customAfter phase separation
  5. extractionthe aqueous phase is back-extracted three times with 250 ml of ethyl acetate each time
  6. washare washed with saturated sodium chloride solution
  7. dry with materialdried over sodium sulfate
  8. customExcess diallyl malonate is subsequently removed by high vacuum distillation (boiling point: 57° C.; 0.074 mbar)
  9. distillationThe distillation residue is purified by flash chromatography on silica gel (mobile phase: cyclohexane/ethyl acetate 2:1)
  10. custom105 g (233 mmol, approx. 60% purity, 43% yield) of a liquid are obtained
  11. customThis product is reacted without further purification in the subsequent stage
  12. customA small amount is purified by preparative HPLC for analytical characterization

Sources & evidence

ORD record
ord-20454def5a0249faa979cda541db4cb1
Source dataset
uspto-grants-2011_08
Patent number
US07998988B2

Reaction notes

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