Methyl acetoacetate → Methyl 3-oxooctadecanoate

HRID 582897Notes

Reaction equation

HRID 582897 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][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24]CC>O1CCCC1>[O:6]=[C:5]([CH2:7][CH2:24][CH2:23][CH2:22][CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH3:11])[CH2:4][C:3]([O:9][CH3:10])=[O:8]

Participants

5

Reactant 3

HCID 7757Methyl acetoacetateHCID 8206Palmitoyl chloride2×HCID 24758Sodium hydride

Product 1

HCID 84501Methyl 3-oxooctadecanoateYield 50%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

A dry tetrahydrofuran suspension (2 l) of 228 g (5.7 mol) of 60% sodium hydride was cooled to 0° C., and 1.8 l of a tetrahydrofuran solution of 638 g (5.5 mol) of methyl acetoacetate was added thereto dropwise, followed by stirring at room temperature for 1 hour. To the mixture was added dropwise 1.511 kg (5.5 mol) of palmitoyl chloride at 0 to 5° C. followed by stirring at room temperature overnight. After confirming disappearance of palmitoyl chloride by TLC, tetrahydrofuran was evaporated, and the residue was poured into ice-water and extracted with 2 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 l of methanol. The mixture was 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. Ethyl acetate was removed by evaporation, and the resulting crude crystals were recrystallized from methanol to give 858 g (2.75 mol; yield: 50.0%) of methyl 3-oxooctadecanoate (melting point: 45° C.).

Workup

  1. stirringby stirring at room temperature overnight
  2. customwas evaporated
  3. additionthe residue was poured into ice-water
  4. extractionextracted with 2 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 l of methanol
  7. temperatureThe mixture was heated 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. customEthyl acetate was removed by evaporation
  13. customthe resulting crude crystals were recrystallized from methanol

Sources & evidence

ORD record
ord-c065b56bb62049a5b156eb104ed14a15
Source dataset
uspto-grants-1999_07
Patent number
US05925792

Reaction notes

Loading…