Methyl acetoacetate → HCID 15107319, compound

HRID 274205Notes

Reaction equation

HRID 274205 reaction equation
[C:1]([O:7][CH3:8])(=[O:6])[CH2:2][C:3]([CH3:5])=[O:4].[H-].[Na+].C([Li])CCC.C([C:18]1[O:22][N:21]=[C:20]([CH:23]([CH3:25])[CH3:24])[CH:19]=1)=O>C1COCC1.CCCCCC.C(O)(=O)C.CO>[CH:23]([C:20]1[CH:19]=[C:18]([CH:8]2[O:7][C:1](=[O:6])[CH2:2][C:3](=[O:4])[CH2:5]2)[O:22][N:21]=1)([CH3:25])[CH3:24]

Participants

9

Reactant 4

HCID 7757Methyl acetoacetateHCID 24758Sodium hydrideHCID 143665615-Isoxazolecarboxaldehyde, 3-(1-methylethyl)- (9CI)HCID 178418339Butyllithium

Product 1

HCID 15107319HCID 15107319, compoundYield 13.5%

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
-60 °C

Procedure

At -10° C., 61.5 g of methyl acetoacetate was dripped into 16.5 g of sodium hydride in 350 ml of THF. The mixture was cooled to -60° C. and 344 ml of 1.6 molar n-butyllithium solution in hexane was added. After all had been added, the mixture was stirred for 30 minutes at -60° C., and then 69.5 g of 5-formyl-3-isopropylisoxazole in 50 ml of THF was quickly dripped in at -60° C. The mixture was stirred for 30 minutes and then 10 ml of methanol followed by 30 g of acetic acid was added. After 10 minutes, the mixture was poured onto 500 g of ice, heated to room temperature, and stirred for 1 hour. The aqueous phase was extracted three times with methylene chloride, brought--with cooling--to a pH of 4.5 with dilute hydrochloric acid, and extracted with methylene chloride. The extract was washed with 5% strength sodium bicarbonate solution and water, dried with sodium sulfate, and the solvent was stripped off in a rotary evaporator. The residue was crystallized by stirring with methyl tert-butyl ether, followed by suction filtration. There was obtained 15 g of pure product.

Workup

  1. customAt -10° C.
  2. additionAfter all had been added
  3. customwas quickly dripped in at -60° C
  4. stirringThe mixture was stirred for 30 minutes
  5. additionwas added
  6. waitAfter 10 minutes
  7. temperatureheated to room temperature
  8. stirringstirred for 1 hour
  9. extractionThe aqueous phase was extracted three times with methylene chloride
  10. temperaturewith cooling
  11. extractionto a pH of 4.5 with dilute hydrochloric acid, and extracted with methylene chloride
  12. washThe extract was washed with 5% strength sodium bicarbonate solution and water
  13. dry with materialdried with sodium sulfate
  14. customthe solvent was stripped off in a rotary evaporator
  15. customThe residue was crystallized
  16. stirringby stirring with methyl tert-butyl ether
  17. filtrationfollowed by suction filtration

Sources & evidence

ORD record
ord-b45c8f0fbb3649d286a257aaa84ffcd2
Source dataset
uspto-grants-1995_02
Patent number
US05389602

Reaction notes

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