tert-Butanol → 2-(2-chloro-4-cyclobutylcarbamoylbenzyl)-3-oxopentanoic Acid Ethyl Ester

HRID 2266628Notes

Reaction equation

HRID 2266628 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:36]=[CH:35][C:27]([C:28]([NH:30][CH:31]2[CH2:34][CH2:33][CH2:32]2)=[O:29])=[CH:26][C:25]=1[Cl:37]>O1CCCC1.O>[CH2:12]([O:14][C:15](=[O:21])[CH:16]([CH2:23][C:24]1[CH:36]=[CH:35][C:27]([C:28](=[O:29])[NH:30][CH:31]2[CH2:34][CH2:33][CH2:32]2)=[CH:26][C:25]=1[Cl:37])[C:17](=[O:20])[CH2:18][CH3:19])[CH3:13]

Participants

7

Reactant 4

HCID 6386tert-ButanolHCID 78656Ethyl 3-oxovalerateHCID 23665647Potassium tert-butoxideHCID 687833844-bromomethyl-3-chloro-N-cyclobutylbenzamide

Product 1

HCID 687826112-(2-chloro-4-cyclobutylcarbamoylbenzyl)-3-oxopentanoic Acid Ethyl Ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A suspension of potassium tert-butoxide (0.34 g) in anhydrous tetrahydrofuran (15 mL) at 0° C. was treated with a mixture of tert-butanol (1.0 mL) and 3-oxopentanoic acid ethyl ester (038 mL). The mixture was stirred at 0° C. for 45 minutes and then a solution of 4-bromomethyl-3-chloro-N-cyclobutylbenzamide (0.67 g) in tetrahydrofuran (5.0 mL) was added and the resulting mixture heated at 70° C. for 24 hours. The mixture was cooled to room temperature, diluted with water and the tetrahydrofuran removed under reduced pressure. The residue was extracted with ethyl acetate and the combined extracts washed With saturated aqueous sodium chloride solution and dried over magnesium sulfate. The solvent was removed under reduced pressure and the residue purified by column chromatography on silica gel, eluting with a mixture of ethyl acetate and cyclohexane (1:5 by volume) to afford title compound, 0.44 g.

Workup

  1. temperaturethe resulting mixture heated at 70° C. for 24 hours
  2. temperatureThe mixture was cooled to room temperature
  3. customthe tetrahydrofuran removed under reduced pressure
  4. extractionThe residue was extracted with ethyl acetate
  5. washthe combined extracts washed With saturated aqueous sodium chloride solution
  6. dry with materialdried over magnesium sulfate
  7. customThe solvent was removed under reduced pressure
  8. customthe residue purified by column chromatography on silica gel
  9. washeluting with a mixture of ethyl acetate and cyclohexane (1:5 by volume)

Sources & evidence

ORD record
ord-7b1a0ac3a00f428ebe2bc60af5163076
Source dataset
uspto-grants-2010_12
Patent number
US07858640B2

Reaction notes

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