반응 #2122491

반응 방정식

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

용매

tetrahydrofuran

diisopropylamine

tetrahydrofuran

반응 조건

후처리

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

실험 절차

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.

출처