Ethyl Acetoacetate → HCID 14851312, compound

HRID 1029465Notes

Reaction equation

HRID 1029465 reaction equation
[H-].[Na+].[C:3]([O:9][CH2:10][CH3:11])(=[O:8])[CH2:4][C:5]([CH3:7])=[O:6].[Li]CCCC.[F:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]2[N:28]([C:29]3[CH:34]=[N:33][CH:32]=[CH:31][N:30]=3)[N:27]=[C:26]([CH:35]([CH3:37])[CH3:36])[C:25]=2/[CH:38]=[CH:39]/[CH:40]=[O:41])=[CH:20][CH:19]=1>C1COCC1>[F:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]2[N:28]([C:29]3[CH:34]=[N:33][CH:32]=[CH:31][N:30]=3)[N:27]=[C:26]([CH:35]([CH3:37])[CH3:36])[C:25]=2/[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])=[CH:20][CH:19]=1

Participants

6

Reactant 4

HCID 8868Ethyl AcetoacetateHCID 24758Sodium hydrideHCID 14851311HCID 14851311, compoundHCID 178418339Butyllithium

Product 1

HCID 14851312HCID 14851312, compoundYield 48.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

To a hexane washed suspension of NaH (0.90 g, 22.5 mmol) in THF (30 mL) at 0° C. under an inert atmosphere, was added a solution of ethyl acetoacetate (2.69 mL, 21.1 mmol) in THF (30 mL). The resulting clear solution was stirred at 0° C. for 15 minutes before n-BuLi (9.6 mL, 21.1 mmol) was added dropwise. The orange solution was stirred at 0° C. for 15 minutes before it was cooled to -78° C. and a solution of the unsaturated aldehyde (4.73 g, 14.1 mmol, Step E) in THF (80 mL) was added dropwise. This was stirred at -78° C. for 2 hours and then it was quenched by adding ~5 mL HOAc and removing the cooling bath. The reaction was partitioned between Et2O and 5% K2CO3 (aq). The organics were dried (MgSO4) and evaporated to give a yellow oil. Elution from a 4-inch silica column gave 3.17 g (48%) of product as a yellow foam.

Workup

  1. washTo a hexane washed
  2. additionwas added dropwise
  3. temperaturewas cooled to -78° C.
  4. stirringThis was stirred at -78° C. for 2 hours
  5. customit was quenched
  6. additionby adding ~5 mL HOAc
  7. customremoving the cooling bath
  8. customThe reaction was partitioned between Et2O and 5% K2CO3 (aq)
  9. dry with materialThe organics were dried (MgSO4)
  10. customevaporated
  11. customto give a yellow oil
  12. washElution from a 4-inch silica column

Sources & evidence

ORD record
ord-17595fb760064b8fb7fe869b62752c51
Source dataset
uspto-grants-1992_04
Patent number
US05102893

Reaction notes

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