Ethyl Acetoacetate → HCID 14851338, compound

HRID 1029469Notes

Reaction equation

HRID 1029469 reaction equation
[H-].[Na+].[C:3]([O:9][CH2:10][CH3:11])(=[O:8])[CH2:4][C:5]([CH3:7])=[O:6].[Li]CCCC.[S:17]1[C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=2[N:19]=[C:18]1[N:26]1[C:30]([C:31]2[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=2)=[C:29](/[CH:38]=[CH:39]/[CH:40]=[O:41])[C:28]([CH:42]([CH3:44])[CH3:43])=[N:27]1>C1COCC1>[S:17]1[C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=2[N:19]=[C:18]1[N:26]1[C:30]([C:31]2[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=2)=[C:29](/[CH:38]=[CH:39]/[CH:40]([OH:41])[CH2:7][C:5](=[O:6])[CH2:4][C:3]([O:9][CH2:10][CH3:11])=[O:8])[C:28]([CH:42]([CH3:44])[CH3:43])=[N:27]1

Participants

6

Reactant 4

HCID 8868Ethyl AcetoacetateHCID 24758Sodium hydrideHCID 14851337HCID 14851337, compoundHCID 178418339Butyllithium

Product 1

HCID 14851338HCID 14851338, compoundYield 87%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

To a hexane washed suspension of NaH (1.23 g, 30.7 mmol) in THF (20 mL) at 0° C. under an inert atmosphere, was added a solution of ethyl acetoacetate (3.66 mL, 28.7 mmol) in THF (20 mL). The resulting clear solution was stirred at 0° C. for 15 minutes before n-BuLi (13.1 mL, 28.7 mmol) was added dropwise. This orange solution was stirred at 0° C. for 15 minutes before it was cooled to -78° C. and a solution of the unsaturated aldehyde (7.50 g, 19.2 mmol, Step E) in THF (100 mL) was added dropwise. The reaction was stirred at -78° C. for 1 hour and then it was quenched by adding 4 mL glacial acetic acid and removing the cooling bath. The reaction mixture was partitioned between Et2O and saturated aqueous K2CO3 solution. The organic extracts were dried (MgSO4) and evaporated to give an orange solid. Recrystallization from hexanes gave 8.71 g (87%) of product as a pale yellow orange solid.

Workup

  1. washTo a hexane washed
  2. additionwas added dropwise
  3. temperaturewas cooled to -78° C.
  4. stirringThe reaction was stirred at -78° C. for 1 hour
  5. customit was quenched
  6. additionby adding 4 mL glacial acetic acid
  7. customremoving the cooling bath
  8. customThe reaction mixture was partitioned between Et2O and saturated aqueous K2CO3 solution
  9. dry with materialThe organic extracts were dried (MgSO4)
  10. customevaporated
  11. customto give an orange solid
  12. customRecrystallization from hexanes

Sources & evidence

ORD record
ord-933a5d3355374970a49f8991ceaa2523
Source dataset
uspto-grants-1992_04
Patent number
US05102893

Reaction notes

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