Diisopropylethylamine → 1-(2-Fluoro-4-nitrophenyl)piperidin-4-one

HRID 2213357Notes

Reaction equation

HRID 2213357 reaction equation
Cl.O.[NH:3]1[CH2:8][CH2:7][C:6](=[O:9])[CH2:5][CH2:4]1.C(N(C(C)C)CC)(C)C.[F:19][C:20]1[CH:21]=[C:22]([N+:27]([O-:29])=[O:28])[CH:23]=[CH:24][C:25]=1F>C(#N)C>[F:19][C:20]1[CH:21]=[C:22]([N+:27]([O-:29])=[O:28])[CH:23]=[CH:24][C:25]=1[N:3]1[CH2:8][CH2:7][C:6](=[O:9])[CH2:5][CH2:4]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 1230531,2-Difluoro-4-nitrobenzeneHCID 2723901Piperonylamine

Product 1

HCID 37637811-(2-Fluoro-4-nitrophenyl)piperidin-4-oneYield 83.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

To a stirring solution of 4-piperidone monohydrate hydrochloride (258.7 g, 1.68 mol) and diisopropylethyl amine (590 ml, 3.39 mol) in acetonitrile (2.5 liter) is added 3,4-difluoronitrobenzene (186.3 ml, 1.68 mol). The mixture is heated to 80° C. and stirred overnight. The solvent is cooled to ambient temperature and removed in vacuo. The residue is partitioned between ethyl acetate and 10% aqueous HCl (1.20 liter each). The layers are shaken, the organic layer separated and washed with 10% HCl and brine (800 ml each). The organic layer is dried over MgSO4 and filtered. As the solvent is removed in vacuo a solid began to precipitate out (˜¼ volume). The resulting slurry is cooled to 0–5° C. and filtered to afford 333.7 g of the title compound. 1H NMR (400 MHz, CDCl3) δ 2.65 (m, 4 H), 3.65 (m, 4 H), 6.98 (m, 1 H), 7.26 (s, 1 H), 8.00 (m, 1 H); Anal. Calcd for C11H11FN2O3: C, 55.46; H, 4.65; N, 11.76. Found: C, 55.34; H, 4.60; N, 11.69.

Workup

  1. temperatureThe solvent is cooled to ambient temperature
  2. customremoved in vacuo
  3. customThe residue is partitioned between ethyl acetate and 10% aqueous HCl (1.20 liter each)
  4. stirringThe layers are shaken
  5. customthe organic layer separated
  6. washwashed with 10% HCl and brine (800 ml each)
  7. dry with materialThe organic layer is dried over MgSO4
  8. filtrationfiltered
  9. customAs the solvent is removed in vacuo a solid
  10. customto precipitate out (˜¼ volume)
  11. temperatureThe resulting slurry is cooled to 0–5° C.
  12. filtrationfiltered

Sources & evidence

ORD record
ord-395af267aed24e839ac6ba46955c68c6
Source dataset
uspto-grants-2006_09
Patent number
US07105547B2

Reaction notes

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