Réaction #2122483

Équation de réaction

(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

Solvants

THF

THF

Conditions de réaction

Traitement

1. 1
   AutreThe suspension obtained
2. 2
   Températurerefluxed under argon for one hour
3. 3
   TempératureAfter 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
   Lavagethe combined organic layers were then washed with brine
8. 8
   Séchagedried over sodium sulfate
9. 9
   FiltrationAfter filtration and concentration under vacuum
10. 10
    Autrethe residue was purified by column chromatography (silica gel, ethyl acetate 100%)

Mode opératoire

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