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

HRID 896172Notes

Reaction equation

HRID 896172 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 stirred solution of 1-(2-fluoro-4-nitrophenyl)piperidin-4-one (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 under reduced pressure. Hexane (4×500 ml) is added and the solvent removed under reduced pressure. At the fourth co-distillation, a slurry forms (˜300 ml). The mixture is cooled to 0° C. and the solids filtered. The filtrate is concentrated to a slurry, cooled and filtered (2nd crop). Solids are combined to give 273.7 g (84%) of the 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, 1 H), 7.67 (d, 1 H), 7.73 (d, 1H).

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 under reduced pressure
  6. additionHexane (4×500 ml) is added
  7. customthe solvent removed under reduced pressure
  8. temperatureThe mixture is cooled to 0° C.
  9. filtrationthe solids filtered
  10. concentrationThe filtrate is concentrated to a slurry
  11. temperaturecooled
  12. filtrationfiltered (2nd crop)

Sources & evidence

ORD record
ord-8ca871616c9842c2b85c7c5daaa68c04
Source dataset
uspto-grants-2005_07
Patent number
US06919329B2

Reaction notes

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