tert-Butanol → 3-Oxo-2-(4-pyrazol-1-ylbenzyl)pentanoic acid ethyl ester

HRID 1922062Notes

Reaction equation

HRID 1922062 reaction equation
CC(C)([O-])C.[K+].C(O)(C)(C)C.[CH2:12]([O:14][C:15](=[O:21])[CH2:16][C:17](=[O:20])[CH2:18][CH3:19])[CH3:13].Br[CH2:23][C:24]1[CH:29]=[CH:28][C:27]([N:30]2[CH:34]=[CH:33][CH:32]=[N:31]2)=[CH:26][CH:25]=1>O1CCCC1.O>[CH2:12]([O:14][C:15](=[O:21])[CH:16]([CH2:23][C:24]1[CH:25]=[CH:26][C:27]([N:30]2[CH:34]=[CH:33][CH:32]=[N:31]2)=[CH:28][CH:29]=1)[C:17](=[O:20])[CH2:18][CH3:19])[CH3:13]

Participants

7

Reactant 4

HCID 6386tert-ButanolHCID 78656Ethyl 3-oxovalerateHCID 27764791-[4-(Bromomethyl)Phenyl]-1H-PyrazoleHCID 23665647Potassium tert-butoxide

Product 1

HCID 674563603-Oxo-2-(4-pyrazol-1-ylbenzyl)pentanoic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A suspension of potassium tert-butoxide (0.57 g) in tetrahydrofuran (40 mL) at 0° C. was treated with a mixture of tert-butanol (2.0 mL) and 3-oxopentanoic acid ethyl ester (0.73 mL), and the resulting mixture was stirred at 0° C. for 45 minutes. The mixture was then treated with a solution of 1-(4-bromomethylphenyl)-1H-pyrazole (1.0 g) in tetrahydrofuran (10 mL), and stirred at 0° C. for 2 hours. The mixture was diluted with water, concentrated to low bulk under reduced pressure, and the residue extracted with ethyl acetate. The combined extracts were washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate and then concentrated under reduced pressure. Purification of the residue by column chromatography on silica gel, eluting with a mixture of cyclohexane and ethyl acetate gave title compound as a pale yellow oil (0.63 g).

Workup

  1. stirringstirred at 0° C. for 2 hours
  2. concentrationconcentrated to low bulk under reduced pressure
  3. extractionthe residue extracted with ethyl acetate
  4. washThe combined extracts were washed with saturated aqueous sodium chloride solution
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customPurification of the residue by column chromatography on silica gel
  8. washeluting with a mixture of cyclohexane and ethyl acetate

Sources & evidence

ORD record
ord-17822fd00a5d4eccad77e6b59ca27202
Source dataset
uspto-grants-2012_05
Patent number
US08173812B2

Reaction notes

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