Réaction #2122491

Équation de réaction

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

Solvants

tetrahydrofuran

diisopropylamine

tetrahydrofuran

Conditions de réaction

Traitement

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

Mode opératoire

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.

Source