Water → 1-(2-Fluoro-4-nitrophenyl)-4-[(trimethylsilyl)oxy]-1,2,3,6-tetrahydropyridine

HRID 2213358Notes

Reaction equation

HRID 2213358 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[CH:4][C:3]=1[N:11]1[CH2:16][CH2:15][C:14](=[O:17])[CH2:13][CH2:12]1.C(N(CC)CC)C.FC(F)(F)S(O[Si:31]([CH3:34])([CH3:33])[CH3:32])(=O)=O.O>C1(C)C=CC=CC=1>[F:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[CH:4][C:3]=1[N:11]1[CH2:12][CH:13]=[C:14]([O:17][Si:31]([CH3:34])([CH3:33])[CH3:32])[CH2:15][CH2:16]1

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 65367Trimethylsilyl triflateHCID 37637811-(2-Fluoro-4-nitrophenyl)piperidin-4-one

Product 1

HCID 218781391-(2-Fluoro-4-nitrophenyl)-4-[(trimethylsilyl)oxy]-1,2,3,6-tetrahydropyridineYield 84%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a stirring solution of the ketone from step 1 (250 g, 1.05 mol) and triethylamine (223 g, 2.20 mol) in toluene (4.2 liter) at 0° C. is slowly added trimethylsilyl trifluoromethanesulfonate (TMS-OTf, 280 g, 1.26 mol) via addition funnel. The stirring is continued for 30 min and the mixture allowed to warm to ambient temperature. Water (5 liter) is added and the aqueous layer extracted with EtOAc (3×500 ml). The organics are combined, dried over MgSO4 and the solvent removed in vacuo. Hexane (4×500 ml) is added and the solvent removed in vacuo. At the fourth co-distillation, a slurry formed (˜300 ml). The mixture is cooled to 0° C. and solids filtered. The filtrated is concentrated to a slurry, cooled and filtered (2nd crop). Solids are combined to result in 273.7 g (84%) title compound as a yellow solid. 1H NMR (CDCl3) δ 0.21 (s, 9 H), 2.20 (brs, 2 H), 3.52 (brs, 2 H), 3.62 (brs, 2 H), 4.89 (brs, 1 H), 6.65 (t, J=8 Hz, 1 H), 7.67 (d, J=12 Hz, 1 H), 7.73 (d, J=12 Hz, 1 H. Anal. Calcd for C14H19FN2O3Si: C, 54.17; H, 6.17; N, 9.02. Found: C, 54.01; H, 6.29; N, 9.15.

Workup

  1. customat 0° C.
  2. additionvia addition funnel
  3. extractionthe aqueous layer extracted with EtOAc (3×500 ml)
  4. dry with materialdried over MgSO4
  5. customthe solvent removed in vacuo
  6. additionHexane (4×500 ml) is added
  7. customthe solvent removed in vacuo
  8. customAt the fourth co-distillation, a slurry formed (˜300 ml)
  9. temperatureThe mixture is cooled to 0° C.
  10. filtrationsolids filtered
  11. concentrationThe filtrated is concentrated to a slurry
  12. temperaturecooled
  13. filtrationfiltered (2nd crop)

Sources & evidence

ORD record
ord-b7ed01cf1b8b40a2a2d0e6d34499a1ce
Source dataset
uspto-grants-2006_09
Patent number
US07105547B2

Reaction notes

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