2-Piperidone → 1-(4-Amino-3-fluoro-phenyl)-piperidin-2-one

HRID 2217460Notes

Reaction equation

HRID 2217460 reaction equation
[F:1][C:2]1[CH:8]=[C:7](I)[CH:6]=[CH:5][C:3]=1[NH2:4].[C:10]1(=[O:16])[NH:15][CH2:14][CH2:13][CH2:12][CH2:11]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].N[C@@H]1CCCC[C@H]1N>CCOC(C)=O.[Cu]I.O1CCOCC1>[NH2:4][C:3]1[CH:5]=[CH:6][C:7]([N:15]2[CH2:14][CH2:13][CH2:12][CH2:11][C:10]2=[O:16])=[CH:8][C:2]=1[F:1]

Participants

8

Reactant 4

HCID 126652-PiperidoneHCID 438061,2-Diaminocyclohexane, trans-HCID 62657Potassium Phosphate, TribasicHCID 1856942-Fluoro-4-iodoaniline

Product 1

HCID 117890101-(4-Amino-3-fluoro-phenyl)-piperidin-2-one

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

2-Fluoro-4-iodoaniline (10.0 g, 42.2 mmol) was combined with δ-valerolactam (6.27 g, 63.3 mmol), CuI (0.804 g, 4.22 mmol), and K3PO4 (22.4 g, 105 mmol). 1,4-Dioxane (60 mL) was added followed by trans-1,2-diaminocyclohexane (1.01 mL, 8.44 mmol). The mixture was heated to reflux for 22 h before cooling and diluting with EtOAc. The mixture was filtered through a plug of silica, eluting with EtOAc, and the filtrate concentrated under reduced pressure. Purification of the crude product by flash chromatography revealed 7 (3.40 g, 39%) as a brown solid. MS: APCI (AP+): 209.1 (M)+.

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 22 h
  3. temperaturebefore cooling
  4. filtrationThe mixture was filtered through a plug of silica
  5. washeluting with EtOAc
  6. concentrationthe filtrate concentrated under reduced pressure
  7. customPurification of the crude product by flash chromatography

Sources & evidence

ORD record
ord-0ca5971259ac457abe84a733bc41a4b7
Source dataset
uspto-grants-2008_08
Patent number
US07407972B2

Reaction notes

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