tert-Butanol → 3-oxo-2-[4-(pyrrolidine-1-carbonyl)benzyl]pentanoic Acid Methyl Ester

HRID 2266603Notes

Reaction equation

HRID 2266603 reaction equation
CC(C)([O-])C.[K+].C(O)(C)(C)C.[CH3:12][O:13][C:14](=[O:20])[CH2:15][C:16](=[O:19])[CH2:17][CH3:18].Cl[CH2:22][C:23]1[CH:28]=[CH:27][C:26]([C:29]([N:31]2[CH2:35][CH2:34][CH2:33][CH2:32]2)=[O:30])=[CH:25][CH:24]=1>O1CCCC1.O>[CH3:12][O:13][C:14](=[O:20])[CH:15]([CH2:22][C:23]1[CH:24]=[CH:25][C:26]([C:29]([N:31]2[CH2:35][CH2:34][CH2:33][CH2:32]2)=[O:30])=[CH:27][CH:28]=1)[C:16](=[O:19])[CH2:17][CH3:18]

Participants

7

Reactant 4

HCID 6386tert-ButanolHCID 121699Methyl 3-oxovalerateHCID 162268621-[4-(Chloromethyl)benzoyl]pyrrolidineHCID 23665647Potassium tert-butoxide

Product 1

HCID 687803523-oxo-2-[4-(pyrrolidine-1-carbonyl)benzyl]pentanoic Acid Methyl Ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A suspension of potassium tert-butoxide (1.4 g) in anhydrous tetrahydrofuran (40 mL) at 0° C. was treated with a mixture of tert-butanol (1.0 mL) and 3-oxopentanoic acid methyl ester (1.3 mL). The mixture was stirred at 0° C. for 45 minutes and then a solution of (4-chloromethylphenyl)pyrrolidin-1-ylmethanone (2.0 g) in tetrahydrofuran (10 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 (3:7 by volume) to afford title compound, 1.1 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 (3:7 by volume)

Sources & evidence

ORD record
ord-953d7b9c7ec74f3189389fe7b6bb39d7
Source dataset
uspto-grants-2010_12
Patent number
US07858640B2

Reaction notes

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