Methanol → 3-Hydroxy-2-methyl-2-phenylpiperidine

HRID 1757240노트

반응식

HRID 1757240 반응식
C(OC([N:8]1[CH2:13][CH2:12][CH2:11][C@@H:10]([O:14]CC2C=CC=C(C#N)C=2)[C@H:9]1[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=O)(C)(C)C.[BH4-].[Na+].[CH3:32]O>>[OH:14][CH:10]1[CH2:11][CH2:12][CH2:13][NH:8][C:9]1([CH3:32])[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1

참가 물질

4

반응물 3

HCID 887MethanolHCID 4311764Sodium borohydrideHCID 53964633(2R*,3R*)-1-t-Butyloxycarbonyl-3-((3-cyanophenyl)methyloxy)-2-phenylpiperidine

생성물 1

HCID 189846243-Hydroxy-2-methyl-2-phenylpiperidine

실험 절차

The ketone of (a) above (3.2 g) was suspended in methanol under nitrogen and the temperature brought to -40° C. Sodium borohydride (0.3 g) was added portionwise. The mixture was stirred for 30 min and then concentrated in vacuo, azeotroping with tetrahydrofuran. Borane tetrahydrofuran complex (64 ml, 1.0M in tetrahydrofuran) was added and the mixture was heated at reflux overnight. The mixture was cooled and quenched carefully with methanol, and the mixture was then concentrated in vacuo. The resulting residue was dissolved in ethanol (100 ml) and potassium carbonate (4.2 g) was added. The mixture was heated at reflux for 12 h. The mixture was cooled and evaporated and the residue was extracted with ethyl acetate and water. The organic extract was washed with brine, dried (MgSO4) and evaporated to afford 3-hydroxy-2-methyl-2-phenylpiperidine as a white solid. 1H NMR (360 MHz, CDCl3) δ7.79 (2H, d, ArH), 7.40 (2H, t, ArH), 7.15-7.19 (1H, m, ArH), 3.89 (1H, mc), 2.89-3.01 (2H, m), 1.67-1.91 (4H, m), 1.39 (3H, s, CH3).

후처리

  1. custombrought to -40° C
  2. concentrationconcentrated in vacuo
  3. customazeotroping with tetrahydrofuran
  4. additionBorane tetrahydrofuran complex (64 ml, 1.0M in tetrahydrofuran) was added
  5. temperaturethe mixture was heated
  6. temperatureat reflux overnight
  7. temperatureThe mixture was cooled
  8. customquenched carefully with methanol
  9. concentrationthe mixture was then concentrated in vacuo
  10. dissolutionThe resulting residue was dissolved in ethanol (100 ml)
  11. additionpotassium carbonate (4.2 g) was added
  12. temperatureThe mixture was heated
  13. temperatureat reflux for 12 h
  14. temperatureThe mixture was cooled
  15. customevaporated
  16. extractionthe residue was extracted with ethyl acetate and water
  17. extractionThe organic extract
  18. washwas washed with brine
  19. dry with materialdried (MgSO4)
  20. customevaporated

출처 및 근거

ORD 기록
ord-196d429f01ae43c7b1d179f6a3a0019d
출처 데이터셋
uspto-grants-1995_08
특허 번호
US05444074

반응 노트

불러오는 중…