Reaction #2563

Reaction equation

4-(4-fluorobenzoyl)piperidine

sodium cyanoborohydride

triethylamine

sodium hydroxide

N-hydroxyethyl-4-methoxy-N-(2-methoxyphenyl)benzene sulfonamide

→

title compound

Yield 20.7%

N-{2-[4-(4-Fluorobenzoyl)piperidino]ethyl}-4-methoxy-N-(2-methoxyphenyl)benzene sulfonamide

Yield 20.7%

Solvents

ether

methanol

acetone

DMSO

DMSO

Conditions

Workup

1. 1
   workup.ADDITIONwas added to the reaction solution
2. 2
   Extractionthe mixture was extracted with ethyl acetate
3. 3
   Washwashed with water and saturated brine
4. 4
   DryingThe resulting organic layer was dried on anhydrous magnesium sulfate
5. 5
   Otherthe solvent was removed by evaporation
6. 6
   Otherto obtain a light yellow oily material
7. 7
   Otherat room temperature
8. 8
   workup.ADDITIONwas added to the reaction mixture which
9. 9
   OtherThe resulting reaction solution
10. 10
    Filtrationfiltered through cerite,
11. 11
    Otherfollowed by the removal of the solvent by evaporation
12. 12
    workup.DISSOLUTIONThe thus obtained colorless oily residue was dissolved in ether (10 ml)
13. 13
    Extractionextracted with 2N hydrochloric acid (10 ml)
14. 14
    OtherAfter removing the ether layer
15. 15
    Otherthe resulting reaction solution
16. 16
    Extractionextracted with methylene chloride
17. 17
    Otherthe resulting organic layer was dried on potassium carbonate
18. 18
    Otherthe solvent was removed by evaporation
19. 19
    OtherThereafter, the resulting yellow oily residue was purified

Procedure

In an atmosphere of argon at room temperature, N-hydroxyethyl-4-methoxy-N-(2-methoxyphenyl)benzene sulfonamide (235 mg, 0.697 mmol) was dissolved in DMSO (3 ml) to which were subsequently added dropwise triethylamine (0.48 ml, 3.44 mmol) and sulfur trioxide-pyridine complex (558 mg, 3.44 mmol) which has been dissolved in DMSO (3 ml). After 20 minutes of stirring at the same temperature, ice water (10 ml) was added to the reaction solution, and the mixture was extracted with ethyl acetate and then washed with water and saturated brine. The resulting organic layer was dried on anhydrous magnesium sulfate, and the solvent was removed by evaporation to obtain a light yellow oily material. The thus obtained residue was dissolved in methanol (5 ml) to which were subsequently added 4-(4-fluorobenzoyl)piperidine (108 mg, 0.52 mmol) and molecular sieve 4A (200 mg) at room temperature. After 45 minutes of stirring at the same temperature, sodium cyanoborohydride (11 mg, 0.166 mmol) was added to the reaction mixture which was stirred for additional 30 minutes, followed by the addition of acetone (1 ml). The resulting reaction solution was diluted with ether (10 ml) and filtered through cerite, followed by the removal of the solvent by evaporation. The thus obtained colorless oily residue was dissolved in ether (10 ml) and extracted with 2N hydrochloric acid (10 ml). After removing the ether layer, the resulting reaction solution was adjusted to pH 9 to 10 with 10% sodium hydroxide aqueous solution and extracted with methylene chloride, the resulting organic layer was dried on potassium carbonate and then the solvent was removed by evaporation. Thereafter, the resulting yellow oily residue was purified by subjecting it to a silica gel column chromatography and PTLC (ether:hexane=7:1) to obtain 56.7 mg (15.4%) of the title compound in the form of colorless oil.

Source