Methanol → N-(4-chloro-3-methyl-5-isoxazolyl)-4-biphenylsulfonamide

HRID 128720노트

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HRID 128720 반응식
[H-].[Na+].[NH2:3][C:4]1[O:8][N:7]=[C:6]([CH3:9])[C:5]=1[Cl:10].[C:11]1([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:16]=[CH:15][C:14]([S:17](Cl)(=[O:19])=[O:18])=[CH:13][CH:12]=1.CO>C1COCC1.O>[Cl:10][C:5]1[C:6]([CH3:9])=[N:7][O:8][C:4]=1[NH:3][S:17]([C:14]1[CH:13]=[CH:12][C:11]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[CH:16][CH:15]=1)(=[O:19])=[O:18]

참가 물질

7

반응물 4

HCID 887MethanolHCID 24758Sodium hydride2회HCID 74192(1,1'-Biphenyl)-4-sulphonyl chlorideHCID 105828224-Chloro-3-methyl-1,2-oxazol-5-amine

생성물 1

HCID 15453176N-(4-chloro-3-methyl-5-isoxazolyl)-4-biphenylsulfonamide수율 83%

시약·촉매·용매 2

HCID 962Water용매HCID 8028Tetrahydrofuran용매2회

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온도
0 °C

실험 절차

Sodium hydride (188 mg, 4.4 mmol) was suspended in dry THF (1 ml) and cooled to 0° C. A solution of 5-amino-4-chloro-3-methylisoxazole (mg, mmol) in dry THF (1 ml) was added with stirring. Once the addition was complete, the reaction mixture was warmed to room temperature for 10 min. The solution was recooled to 0° C., and 4-biphenylsulfonyl chloride (0.283 ml, 2.2 mmol) was added. Stirring was continued at 25° C. for 2 h. Excess sodium hydride was decomposed by the addition of methanol (0.4 ml) followed by water (0.5 ml). THF was removed under reduced pressure and the residue was dissolved in water (20 ml) and basified by addition of sodium hydroxide (pH 9-10). Neutral impurities were removed by extraction with ethyl acetate (2×10 ml). The aqueous layer was acidified to pH 2-3 using concentrated HCl and extracted with ethyl acetate (3×10 ml). The combined organic layer was dried over magnesium sulfate. Removal of the solvent gave N-(4-chloro-3-methyl-5-isoxazolyl)-4-biphenylsulfonamide in 83% yield. This product was purified by recrystallization from ethyl acetate/hexanes as a white solid, m.p. 129°-132° C.

후처리

  1. additionOnce the addition
  2. temperaturethe reaction mixture was warmed to room temperature for 10 min
  3. customwas recooled to 0° C.
  4. stirringStirring
  5. customTHF was removed under reduced pressure
  6. dissolutionthe residue was dissolved in water (20 ml)
  7. additionbasified by addition of sodium hydroxide (pH 9-10)
  8. customNeutral impurities were removed by extraction with ethyl acetate (2×10 ml)
  9. extractionextracted with ethyl acetate (3×10 ml)
  10. dry with materialThe combined organic layer was dried over magnesium sulfate
  11. customRemoval of the solvent

출처 및 근거

ORD 기록
ord-88cc0889bb6c4ed0a0839e066373c6ff
출처 데이터셋
uspto-grants-1995_11
특허 번호
US05464853

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