Reacción #2122483

Ecuación de reacción

(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

Disolventes

THF

THF

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroThe suspension obtained
2. 2
   Temperaturarefluxed under argon for one hour
3. 3
   TemperaturaAfter cooling to room temperature
4. 4
   Concentraciónthe reaction mixture was concentrated
5. 5
   workup.ADDITIONwater was added
6. 6
   ExtracciónThe aqueous layer was extracted with dichloromethane
7. 7
   Lavadothe combined organic layers were then washed with brine
8. 8
   Secadodried over sodium sulfate
9. 9
   FiltraciónAfter filtration and concentration under vacuum
10. 10
    Otrothe residue was purified by column chromatography (silica gel, ethyl acetate 100%)

Procedimiento

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.

Fuente