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

HRID 2292985Notes

Reaction equation

HRID 2292985 reaction equation
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

Participants

10

Reactant 6

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

Product 1

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

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-70 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-120c22a47c9042d1ab80073ebe52ada8
Source dataset
uspto-grants-1997_11
Patent number
US05684195

Reaction notes

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