반응 #938205

ord-fc517e00166244ca8e72bf308edf9e06

용매

반응 조건

온도
90°CELSIUS
상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    온도cooled to room temperature
  2. 2
    온도The mixture is cooled
  3. 3
    기타partitioned between ether and saturated aqueous NaCl solution
  4. 4
    추출The aqueous phase is extracted with ether
  5. 5
    세척the combined ether extracts are washed with water and saturated aqueous NaCl solution
  6. 6
    농축concentrated in vacuo to an oil
  7. 7
    workup.DISSOLUTIONThis material is dissolved in 200 ml of dichloromethane
  8. 8
    추출the solution is extracted with 2 N HCl solution
  9. 9
    세척The dichloromethane phase is successively washed with 10% aqueous NaOH solution, water, saturated aqueous NaCl solution
  10. 10
    건조dried over anhydrous Na2SO4
  11. 11
    농축concentrated in vacuo
  12. 12
    기타to afford an oil which
  13. 13
    기타crystallizes
  14. 14
    기타This material is chromatographed on silica gel

실험 절차

A mixture of 0.6 g of sodium hydride, 3.83 g of sodium hydride, 3.83 g of trans-1-methyl-3-phenyl-4-piperidinol of Example 1 and 30 ml of anhydrous DMF is heated to 90° C. for 1.5 hours, then cooled to room temperature. A solution of 2.85 g of p-difluorobenzene in 20 ml of DMF is added all at once; the mixture is stirred at 70°-80° C. under nitrogen for 48 hours. The mixture is cooled and partitioned between ether and saturated aqueous NaCl solution. The aqueous phase is extracted with ether, and the combined ether extracts are washed with water and saturated aqueous NaCl solution and then concentrated in vacuo to an oil. This material is dissolved in 200 ml of dichloromethane, and the solution is extracted with 2 N HCl solution. The dichloromethane phase is successively washed with 10% aqueous NaOH solution, water, saturated aqueous NaCl solution, dried over anhydrous Na2SO4, and concentrated in vacuo to afford an oil which crystallizes upon standing. This material is chromatographed on silica gel, using acetone and then 25% methanol/acetone as solvent to obtain trans-4-(4-fluorophenoxy)-1-methyl-3-phenylpiperidine, m.p. s 67°, 69.5°-71.5° C.

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: US04382141uspto-grants-1983_05