Reacción #2122491

Ecuación de reacción

n-butyllithium

(2,4,6-trimethyl-phenyl)-acetic acid methyl ester

1-methoxy-4-(4-methoxybenzylsulfanyl)-piperidine-4-carbonyl chloride

→

3-[1-methoxy-4-(4-methoxy-benzylsulfanyl)-piperidin-4-yl]-3-oxo-2-(2,4,6-trimethylphenyl)-propionic acid methyl ester

Disolventes

tetrahydrofuran

diisopropylamine

tetrahydrofuran

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.STIRRINGthe mixture stirred for additional 30 minutes at 0° C
2. 2
   workup.ADDITIONadded to the reaction mixture, which
3. 3
   Temperaturato warm to room temperature
4. 4
   workup.STIRRINGstirred for 18 hours
5. 5
   OtroThe solvent was evaporated
6. 6
   Otrothe residue partitioned between half saturated aqueous ammonium chloride and t-butylmethyl ether
7. 7
   Lavadothe organic layer washed with brine
8. 8
   Secadodried over sodium sulfate
9. 9
   Otroevaporated
10. 10
    OtroThe residue was chromatographed on silica gel with ethyl acetate/cyclohexane (1:9

Procedimiento

In a separate flask, 512 mg diisopropylamine was dissolved in 15 ml tetrahydrofuran, cooled to −5° C., and 2.86 ml n-butyllithium (1.6M in hexane) was added, then stirred at 0° C. for 1 hour. Then 864 mg (2,4,6-trimethyl-phenyl)-acetic acid methyl ester was added, and the mixture stirred for additional 30 minutes at 0° C. The crude 1-methoxy-4-(4-methoxybenzylsulfanyl)-piperidine-4-carbonyl chloride was dissolved in 5 ml tetrahydrofuran and added to the reaction mixture, which was then allowed to warm to room temperature and stirred for 18 hours. The solvent was evaporated, the residue partitioned between half saturated aqueous ammonium chloride and t-butylmethyl ether, the organic layer washed with brine, dried over sodium sulfate, and evaporated. The residue was chromatographed on silica gel with ethyl acetate/cyclohexane (1:9, then 1:5, then 1:2) as a solvent. Thus, 508 mg 3-[1-methoxy-4-(4-methoxy-benzylsulfanyl)-piperidin-4-yl]-3-oxo-2-(2,4,6-trimethylphenyl)-propionic acid methyl ester was obtained.

Fuente