Ethyl Acetoacetate → HCID 15748275, compound

HRID 1029473Notes

Reaction equation

HRID 1029473 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:38]=[CH:37][C:36]4[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=4)[N:30]=3)[N:27]=[C:26]([CH:39]([CH3:41])[CH3:40])[C:25]=2/[CH:42]=[CH:43]/[CH:44]=[O:45])=[CH:20][CH:19]=1>C1COCC1.CCCCCC>[F:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]2[N:28]([C:29]3[CH:38]=[CH:37][C:36]4[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=4)[N:30]=3)[N:27]=[C:26]([CH:39]([CH3:41])[CH3:40])[C:25]=2/[CH:42]=[CH:43]/[CH:44]([OH:45])[CH2:7][C:5](=[O:6])[CH2:4][C:3]([O:9][CH2:10][CH3:11])=[O:8])=[CH:20][CH:19]=1

Participants

7

Reactant 4

HCID 8868Ethyl AcetoacetateHCID 24758Sodium hydrideHCID 15748272HCID 15748272, compoundHCID 178418339Butyllithium

Product 1

HCID 15748275HCID 15748275, compoundYield 90%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent4×HCID 8058HexaneSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred suspension of hexane washed NaH (0.77 g, 19.1 mmoles) in 30 mL THF at 0° C. under a nitrogen atmosphere, was added dropwise a solution of ethyl acetoacetate (2.27 mL, 17.9 mmoles) in 30 mL THF. The mixture was stirred for 15 minutes before a 2.2 M solution of n-BuLi (8.2 mL, 17.9 mmoles) in THF was added dropwise via syringe. The resulting orange solution was stirred at 0° C. for 15 minutes and then cooled to -7S° C. A solution of trans-3-[5-(4-fluorophenyl)-3-(l-methylethyl)-1-(2-quinolinyl)-1H-pyrazol-4-yl]-2-propenal (4.61 g, 12.0 mmoles) in 50 mL THF was added dropwise and after 2 hours at -78° C. the reaction was quenched by adding 6 mL glacial HOAc and removing the cooling bath. The reaction was partitioned between 5% K2CO3 and Et2O. The organic layer was dried over MgSO4, filtered, and evaporated to give an orange oil. Chromatography (SiO2, 20% EtOAc/hexanes) gave 5.57 g (90%) of the title compound as a yellow solid, mp 47°-53° C.

Workup

  1. additionwas added dropwise via syringe
  2. temperaturecooled to -7S° C
  3. customwas quenched
  4. additionby adding 6 mL glacial HOAc
  5. customremoving the cooling bath
  6. customThe reaction was partitioned between 5% K2CO3 and Et2O
  7. dry with materialThe organic layer was dried over MgSO4
  8. filtrationfiltered
  9. customevaporated
  10. customto give an orange oil

Sources & evidence

ORD record
ord-1f6aff26da5d4771b4c33e5709390c0a
Source dataset
uspto-grants-1992_04
Patent number
US05102893

Reaction notes

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