Acetic Acid → HCID 12595611, compound

HRID 2059903Notes

Reaction equation

HRID 2059903 reaction equation
[C:1](O)(=O)[CH3:2].[O:5]1[C:9]2([CH2:14][CH2:13][C:12](=O)[CH2:11][CH2:10]2)[O:8][CH2:7][CH2:6]1.[CH3:16][NH:17][CH3:18].[C-]#N.[K+]>CO>[CH3:16][N:17]([CH3:18])[C:12]1([C:2]2[CH:1]=[CH:11][CH:10]=[CH:9][CH:14]=2)[CH2:13][CH2:14][C:9]2([O:8][CH2:7][CH2:6][O:5]2)[CH2:10][CH2:11]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 674DimethylamineHCID 9032Potassium CyanideHCID 5674151,4-Dioxaspiro[4.5]decan-8-one

Product 1

HCID 12595611HCID 12595611, compoundYield 59%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

Acetic acid (30 ml) was added to a solution of 1,4-dioxaspiro[4.5]decan-8-one (128 mmol) in methanol (50 ml). The reaction mixture was cooled to 0° C. and dimethylamine solution (200 ml, 40% eq) was added dropwise. Potassium cyanide (2 eq) was added at the same temperature, then the cooling bath was removed and the reaction mixture stirred for 15 h at room temperature. It was hydrolysed with ammonium hydroxide solution (50% eq, 800 ml) and stirred for 1 h, then diluted with ethyl acetate. After phase separation the organic phase was washed with water, saturated sodium chloride solution and saturated iron sulfate solution and concentrated to small volume under vacuum. The crude dimethylaminonitrile intermediate (16 g) was dissolved in tetrahydrofuran (200 ml), cooled, and phenyl magnesium chloride solution (760 ml, 1 mol/l in hexane) was added dropwise. The cooling bath was removed and the reaction mixture stirred overnight at room temperature. It was hydrolysed with saturated ammonium chloride solution and diluted with ethyl acetate. After phase separation the organic phase was washed with water and saturated sodium chloride solution, dried over sodium sulfate and concentrated to small volume under vacuum. The crude product was purified by column chromatography (silica gel) with methanol/DCM. Yield: 59%

Workup

  1. customthe cooling bath was removed
  2. stirring800 ml) and stirred for 1 h
  3. additiondiluted with ethyl acetate
  4. customAfter phase separation the organic phase
  5. washwas washed with water, saturated sodium chloride solution and saturated iron sulfate solution
  6. concentrationconcentrated to small volume under vacuum
  7. dissolutionThe crude dimethylaminonitrile intermediate (16 g) was dissolved in tetrahydrofuran (200 ml)
  8. temperaturecooled
  9. additionphenyl magnesium chloride solution (760 ml, 1 mol/l in hexane) was added dropwise
  10. customThe cooling bath was removed
  11. stirringthe reaction mixture stirred overnight at room temperature
  12. additiondiluted with ethyl acetate
  13. customAfter phase separation the organic phase
  14. washwas washed with water and saturated sodium chloride solution
  15. dry with materialdried over sodium sulfate
  16. concentrationconcentrated to small volume under vacuum
  17. customThe crude product was purified by column chromatography (silica gel) with methanol/DCM

Sources & evidence

ORD record
ord-1fdf29c2b5dd46dfa5ad347e70df7402
Source dataset
uspto-grants-2012_10
Patent number
US08278319B2

Reaction notes

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