반응 #2563

반응 방정식

4-(4-fluorobenzoyl)piperidine

sodium cyanoborohydride

triethylamine

sodium hydroxide

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

→

title compound

수율 20.7%

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

수율 20.7%

용매

ether

methanol

acetone

DMSO

DMSO

반응 조건

후처리

1. 1
   workup.ADDITIONwas added to the reaction solution
2. 2
   추출the mixture was extracted with ethyl acetate
3. 3
   세척washed with water and saturated brine
4. 4
   건조The resulting organic layer was dried on anhydrous magnesium sulfate
5. 5
   기타the solvent was removed by evaporation
6. 6
   기타to obtain a light yellow oily material
7. 7
   기타at room temperature
8. 8
   workup.ADDITIONwas added to the reaction mixture which
9. 9
   기타The resulting reaction solution
10. 10
    여과filtered through cerite,
11. 11
    기타followed 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
    추출extracted with 2N hydrochloric acid (10 ml)
14. 14
    기타After removing the ether layer
15. 15
    기타the resulting reaction solution
16. 16
    추출extracted with methylene chloride
17. 17
    기타the resulting organic layer was dried on potassium carbonate
18. 18
    기타the solvent was removed by evaporation
19. 19
    기타Thereafter, the resulting yellow oily residue was purified

실험 절차

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.

출처