Reaction #2122491

Reaction equation

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

Solvents

tetrahydrofuran

diisopropylamine

tetrahydrofuran

Conditions

Workup

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

Procedure

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