Ethyl 2-chloroacetoacetate → HCID 22499791, compound

HRID 1815121Notes

Reaction equation

HRID 1815121 reaction equation
[H-].[Na+].C([O:5][C:6](=O)[CH:7]([Cl:11])[C:8]([CH3:10])=[O:9])C.C([Li])CCC.[CH:18]1([C:23](=[O:28])[CH2:24][CH2:25][C:26]#[CH:27])[CH2:22][CH2:21][CH2:20][CH2:19]1>C1COCC1>[CH2:24]([C:23]1([CH:18]2[CH2:22][CH2:21][CH2:20][CH2:19]2)[O:28][C:6](=[O:5])[CH:7]([Cl:11])[C:8](=[O:9])[CH2:10]1)[CH2:25][C:26]#[CH:27]

Participants

6

Reactant 4

HCID 11858Ethyl 2-chloroacetoacetateHCID 24758Sodium hydrideHCID 224997991-Cyclopentyl-pent-4-yn-1-oneHCID 178418339Butyllithium

Product 1

HCID 22499791HCID 22499791, compoundYield 76.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-40 °C

Procedure

To a slurry of sodium hydride (480 mg, 60% suspension in mineral oil, 12 mmol) in THF (30 mL) cooled to −10° C. was added ethyl-2-chloroacetoacetate (1.66 mL, 12 mmol). The reaction was stirred until all gas evolution ceased. The reaction was then cooled to −40 ° C. and a solution of butyl lithium (4.8 mL, 2.5 M in ether, 12 mmol) was added. The reaction was stirred for 10 minutes, and then 1-cyclopentyl-pent-4-yn-1-one (0.60 g, 4 mmol) was added as a solution in THF (10 mL). The reaction was stirred for 1 hour, and then quenched with 40 mL saturated ammonium chloride. The solution was acidified further with 5 mL of 6 N HCl. The layers were separated, and the aqueous was extracted with ethyl acetate. The organics were combined and washed with water and then saturated sodium chloride. The organic phase was dried over sodium sulfate, filtered, and then concentrated. The crude product was then dissolved in toluene (13 mL) and bis(dibutylchlorotin) (1.027 g) was added. The solution was heated to reflux for one hour. The reaction was then concentrated and chromatographed (40 g silica gel, 2% MeOH in CH2Cl2) to yield the title compound (0.820 g, 76%).

Workup

  1. stirringThe reaction was stirred for 10 minutes
  2. stirringThe reaction was stirred for 1 hour
  3. customquenched with 40 mL saturated ammonium chloride
  4. customThe layers were separated
  5. extractionthe aqueous was extracted with ethyl acetate
  6. washwashed with water
  7. dry with materialThe organic phase was dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. dissolutionThe crude product was then dissolved in toluene (13 mL)
  11. additionbis(dibutylchlorotin) (1.027 g) was added
  12. temperatureThe solution was heated
  13. temperatureto reflux for one hour
  14. concentrationThe reaction was then concentrated
  15. customchromatographed (40 g silica gel, 2% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-6b7831eb8f16419eafb2d5c1349f0d51
Source dataset
uspto-grants-2005_04
Patent number
US06878727B2

Reaction notes

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