Caprolactam → 1-(4-Fluorophenyl)azepan-2-one

HRID 2241377Notes

Reaction equation

HRID 2241377 reaction equation
[C:1]1(=[O:8])[NH:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[F:9][C:10]1[CH:15]=[CH:14][C:13](I)=[CH:12][CH:11]=1.N1CCC[C@H]1C(O)=O.C([O-])([O-])=O.[K+].[K+]>CS(C)=O.O>[F:9][C:10]1[CH:15]=[CH:14][C:13]([N:7]2[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][C:1]2=[O:8])=[CH:12][CH:11]=1

Participants

7

Reactant 4

HCID 7768CaprolactamHCID 96054-FluoroiodobenzeneHCID 11430Potassium CarbonateHCID 145742L-Proline

Product 1

HCID 675158001-(4-Fluorophenyl)azepan-2-oneYield 6.4%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A suspension of ε-caprolactam (10 g, 90 mmol), 1-fluoro-4-iodobenzene (10 ml, 90 mmol), L-proline (4.1 g, 36 mmol), K2CO3 (37 g, 270 mmol), and Cu(I)I (3.4 g, 18 mmol) was stirred in DMSO (50 mL) and heated to 100° C. for 12 hours. Water (50 mL) was added and the reaction mixture was extracted with EtOAc. The organic layer washed with water) and brine, dried with Na2SO4, filtered and concentrated. The residue was purified by silica gel chromatography (50% EtOAc in hexane) to afford the product (1.2 g, 6.4% yield) as brown oil. LRMS (APCI pos) m/e 208.0 (M+1).

Workup

  1. extractionthe reaction mixture was extracted with EtOAc
  2. washThe organic layer washed with water) and brine
  3. dry with materialdried with Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel chromatography (50% EtOAc in hexane)

Sources & evidence

ORD record
ord-1249300f54324a32a3dfd92a5c318495
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

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