tert-Butanol → 2-(4-Methoxybenzyl)-3-oxopentanoic acid ethyl ester

HRID 1922071Notes

Reaction equation

HRID 1922071 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].Cl[CH2:23][C:24]1[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=1>O1CCCC1.[Cl-].[NH4+]>[CH2:12]([O:14][C:15](=[O:21])[CH:16]([CH2:23][C:24]1[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=1)[C:17](=[O:20])[CH2:18][CH3:19])[CH3:13]

Participants

7

Reactant 4

HCID 6386tert-ButanolHCID 699934-Methyloxybenzyl chlorideHCID 78656Ethyl 3-oxovalerateHCID 23665647Potassium tert-butoxide

Product 1

HCID 674564652-(4-Methoxybenzyl)-3-oxopentanoic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of potassium tert-butoxide (5.4 g), tetrahydrofuran (80 mL), tert-butanol (0.1 mL) and 3-oxopentanoic acid ethyl ester (5.0 g) at 0° C. was treated with a solution of 1-chloromethyl-4-methoxybenzene (4.7 mL) in tetrahydrofuran (20 mL), and the resulting mixture was stirred at 0° C. for 30 minutes, and then at room temperature for 24 hours. The mixture was diluted with saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The combined extracts were dried over sodium sulfate and the solvent removed under reduced pressure. Purification of the residue by column chromatography on silica gel, eluting with a mixture of pentane and ethyl acetate (1:0 to 0:1 by volume), followed by distillation under reduced pressure (150° C., 1 mbar) gave title compound as a colourless oil (3.0 g). 1H NMR analysis showed that the product existed as a mixture of keto and enol isomers.

Workup

  1. waitat room temperature for 24 hours
  2. extractionextracted with ethyl acetate
  3. dry with materialThe combined extracts were dried over sodium sulfate
  4. customthe solvent removed under reduced pressure
  5. customPurification of the residue by column chromatography on silica gel
  6. washeluting with a mixture of pentane and ethyl acetate (1:0 to 0:1 by volume)
  7. distillationfollowed by distillation under reduced pressure (150° C., 1 mbar)

Sources & evidence

ORD record
ord-83b912c393ce4559ae8097032aba92e4
Source dataset
uspto-grants-2012_05
Patent number
US08173812B2

Reaction notes

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