Methyl acetoacetate → Decanoic acid, 3-oxo-, methyl ester

HRID 582888Notes

Reaction equation

HRID 582888 reaction equation
[H-].[Na+].[C:3]([O:9][CH3:10])(=[O:8])[CH2:4][C:5]([CH3:7])=[O:6].[C:11](Cl)(=O)[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16]CC>O1CCCC1>[O:6]=[C:5]([CH2:7][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16])[CH2:4][C:3]([O:9][CH3:10])=[O:8]

Participants

5

Reactant 3

HCID 7757Methyl acetoacetateHCID 8124Octanoyl chloride2×HCID 24758Sodium hydride

Product 1

HCID 89669Decanoic acid, 3-oxo-, methyl esterYield 55%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

A dry tetrahydrofuran suspension (4 l) containing 440 g (11 mol) of 60% sodium hydride was cooled to 0° C., and 1.8 l of a tetrahydrofuran solution of 1.161 kg (10 mol) of methyl acetoacetate was added thereto dropwise, followed by stirring at room temperature for 1 hour. To the reaction mixture was added dropwise 1.789 kg (11 mol) of octanoyl chloride at 0 to 5° C., followed by stirring at room temperature overnight. After confirming disappearance of the octanoyl chloride by thin layer chromatography (TLC), tetrahydrofuran was evaporated, and the residue was poured into ice-water and extracted with 8 l of ethyl acetate. Ethyl acetate was evaporated, and the residue was poured into a mixture of 400 g of a 28% methanol solution of sodium methoxide and 1.2 e of methanol and heated at 60 to 65° C. for 6 hours while stirring to conduct deacylation. The product was cooled with ice, adjusted to pH 5 with a 10% sulfuric acid aqueous solution, and extracted with ethyl acetate. The ethyl acetate layer was washed successively with a 5% sodium carbonate aqueous solution and a saturated sodium chloride aqueous solution. The ethyl acetate was evaporated, and the concentrated residue was distilled under reduced pressure to give 1.10 kg (5.5 mol; yield: 50%) of methyl 3-oxodecanoate (boiling point: 121° C./5 mmHg).

Workup

  1. stirringby stirring at room temperature overnight
  2. customwas evaporated
  3. additionthe residue was poured into ice-water
  4. extractionextracted with 8 l of ethyl acetate
  5. customEthyl acetate was evaporated
  6. additionthe residue was poured into a mixture of 400 g of a 28% methanol solution of sodium methoxide and 1.2 e of methanol
  7. temperatureheated at 60 to 65° C. for 6 hours
  8. stirringwhile stirring
  9. temperatureThe product was cooled with ice
  10. extractionextracted with ethyl acetate
  11. washThe ethyl acetate layer was washed successively with a 5% sodium carbonate aqueous solution
  12. customThe ethyl acetate was evaporated
  13. distillationthe concentrated residue was distilled under reduced pressure

Sources & evidence

ORD record
ord-22d9856e86134728b78ada437bb448cc
Source dataset
uspto-grants-1999_07
Patent number
US05925792

Reaction notes

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