Hexane → 4-[4-(4-Fluorophenyl)thien-3-yl]benzenesulfonamide

HRID 2292985노트

반응식

HRID 2292985 반응식
C[S:2]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[C:15]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)=[CH:14][S:13][CH:12]=2)=[CH:7][CH:6]=1)(=[O:4])=[O:3].C([Li])CCC.CCCCCC.C(B(CCCC)CCCC)CCC.C([O-])(=O)C.[Na+].[NH2:52]OS(O)(=O)=O>C1COCC1.C(OCC)(=O)C.O>[F:22][C:19]1[CH:20]=[CH:21][C:16]([C:15]2[C:11]([C:8]3[CH:9]=[CH:10][C:5]([S:2]([NH2:52])(=[O:4])=[O:3])=[CH:6][CH:7]=3)=[CH:12][S:13][CH:14]=2)=[CH:17][CH:18]=1

참가 물질

10

반응물 6

HCID 8058HexaneHCID 31216TributylboraneHCID 76284hydroxylamine-O-sulfonic acidHCID 517045Sodium AcetateHCID 104268843-(4-Methylsulfonylphenyl)-4-(4-fluorophenyl)thiopheneHCID 178418339Butyllithium

생성물 1

HCID 120886704-[4-(4-Fluorophenyl)thien-3-yl]benzenesulfonamide수율 17.7%

시약·촉매·용매 3

HCID 962Water용매HCID 8028Tetrahydrofuran용매2회HCID 8857Ethyl Acetate용매

반응 조건

온도
-70 °C

실험 절차

To a solution of 3-(4-methylsulfonylphenyl)-4-(4-fluorophenyl)thiophene (0.332 g, 1.0 mmol) from Step 5 in THF (8 mL) at -70° C. under nitrogen was added 1.6M n-butyllithium in hexane (0.66 mL, 1.05 mmol) slowly, via syringe, and the mixture stirred at -70° C. for 20 minutes and then at room temperature (25° C.) for 1 hour. After cooling to -70° C., a 1.0M solution of tri-n-butyl borane in THF (1.15 mL, 1.15 mmol) was added and the mixture allowed to warm slowly to 0° C. for 1 hour, warmed to room temperature for 2 hours, and finally stirred at reflux overnight (18 hours). After cooling to room temperature and stirring for 3 hours, water (0.8 mL) was added followed by sodium acetate (0.6 g) and hydroxylamine-O-sulfonic acid (0.41 g). After stirring at room temperature overnight, the mixture was poured into 3 volumes of ethyl acetate, and the organic layer washed with water and brine and dried over MgSO4. After solvent removal, the white solids (a mixture of product and starting material) were separated via flash chromatography on silica gel using a 15% ethyl acetate/85% toluene eluant to yield 4-[4-(4-fluorophenyl)thien-3-yl]benzenesulfonamide as a white solid (59 mg, mp 194°-195° C.). Anal. Calc'd for C16 H12NO2S2F: C, 57.64; H, 3.63; N, 4.20. Found: C, 57.37; H, 3.69; N, 3.99.

후처리

  1. waitat room temperature (25° C.) for 1 hour
  2. temperatureAfter cooling to -70° C.
  3. temperatureto warm slowly to 0° C. for 1 hour
  4. temperaturewarmed to room temperature for 2 hours
  5. stirringfinally stirred
  6. temperatureat reflux overnight (18 hours)
  7. temperatureAfter cooling to room temperature
  8. stirringstirring for 3 hours
  9. stirringAfter stirring at room temperature overnight
  10. washthe organic layer washed with water and brine
  11. dry with materialdried over MgSO4
  12. customAfter solvent removal
  13. additionthe white solids (a mixture of product and starting material)
  14. customwere separated via flash chromatography on silica gel using a 15% ethyl acetate/85% toluene eluant

출처 및 근거

ORD 기록
ord-120c22a47c9042d1ab80073ebe52ada8
출처 데이터셋
uspto-grants-1997_11
특허 번호
US05684195

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