Reaction #2122483

Reaction equation

(2,4,5-trimethyl-phenyl)acetic acid methyl ester

4-hydroxy-1-methoxy-piperidine-4-carboxylic acid ethyl ester

potassium tert-butoxide

→

4-Hydroxy-8-methoxy-3-(2,4,5-trimethyl-phenyl)-1-oxa-8-aza-spiro[4.5]dec-3-en-2-one

Solvents

THF

THF

Conditions

Workup

1. 1
   OtherThe suspension obtained
2. 2
   Temperaturerefluxed under argon for one hour
3. 3
   TemperatureAfter cooling to room temperature
4. 4
   Concentrationthe reaction mixture was concentrated
5. 5
   workup.ADDITIONwater was added
6. 6
   ExtractionThe aqueous layer was extracted with dichloromethane
7. 7
   Washthe combined organic layers were then washed with brine
8. 8
   Dryingdried over sodium sulfate
9. 9
   FiltrationAfter filtration and concentration under vacuum
10. 10
    Otherthe residue was purified by column chromatography (silica gel, ethyl acetate 100%)

Procedure

To a solution of (2,4,5-trimethyl-phenyl)acetic acid methyl ester (0.6 g, 3.12 mmol) and 4-hydroxy-1-methoxy-piperidine-4-carboxylic acid ethyl ester (0.76 g, 3.74 mmol) in 7 ml anhydrous THF was added a 1 M solution of potassium tert-butoxide (6.9 ml, 8.87 mmol) in THF at room temperature. The suspension obtained was first stirred at room temperature for one hour, and then refluxed under argon for one hour. After cooling to room temperature, the reaction mixture was concentrated, water was added and the mixture acidified with little HCl (37%). The aqueous layer was extracted with dichloromethane, and the combined organic layers were then washed with brine and dried over sodium sulfate. After filtration and concentration under vacuum, the residue was purified by column chromatography (silica gel, ethyl acetate 100%). Yield: 280 mg of 4-hydroxy-8-methoxy-3-(2,4,5-trimethyl-phenyl)-1-oxa-8-aza-spiro[4.5]dec-3-en-2-one (title compound P2.2) as a white solid, mp 199-204° C.

Source