Reaktion #2122491

Reaktionsgleichung

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

Lösungsmittel

tetrahydrofuran

diisopropylamine

tetrahydrofuran

Reaktionsbedingungen

Aufarbeitung

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

Vorschrift

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.

Quelle