Caprolactam → 1-(1-methyl-4-nitro-1H-pyrazol-5-yl)azepan-2-one

HRID 1915804Notes

Reaction equation

HRID 1915804 reaction equation
[NH:1]1[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][C:2]1=[O:8].Br[C:10]1[N:14]([CH3:15])[N:13]=[CH:12][C:11]=1[N+:16]([O-:18])=[O:17].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:15][N:14]1[C:10]([N:1]2[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][C:2]2=[O:8])=[C:11]([N+:16]([O-:18])=[O:17])[CH:12]=[N:13]1

Participants

7

Reactant 4

HCID 7768CaprolactamHCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 12795875-bromo-1-methyl-4-nitro-1H-pyrazole

Product 1

HCID 866800121-(1-methyl-4-nitro-1H-pyrazol-5-yl)azepan-2-oneYield 44.9%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of azepan-2-one (136 mg, 1.2 mmol), 5-bromo-1-methyl-4-nitro-1H-pyrazole (206 mg, 1.0 mmol), Xantphos (116 mg, 0.20 mmol) and caesium carbonate (456 mg, 1.40 mmol) in dioxane (4 mL) was degassed by bubbling nitrogen through it for 15 min. Tris(dibenzylideneacetone)dipalladium(0) (46 mg, 0.05 mmol) was then added and the mixture degassed for a further 10 min before being heated in the microwave at 140° C. for 3 hours. Water (10 mL) was added and the mixture extracted into EtOAc (3×10 mL). The combined organic layers were passed through a phase separation cartridge and concentrated under reduced pressure. The residue was purified via silica gel chromatography (0-100% EtOAc/isohexane) to give 1-(1-methyl-4-nitro-1H-pyrazol-5-yl)azepan-2-one as a brown gum (107 mg, 44%). 1H NMR (400 MHz, CDCl3) δ 8.11 (s, 1H), 3.96 (dd, J=15.2, 10.0 Hz, 1H), 3.76 (s, 3H), 3.53 (dd, J=15.2, 7.2 Hz, 1H), 2.82-2.74 (m, 2H), 2.13-1.96 (m, 3H), 1.83-1.67 (m, 3H).

Workup

  1. customwas degassed
  2. customby bubbling nitrogen through it for 15 min
  3. customthe mixture degassed for a further 10 min
  4. additionWater (10 mL) was added
  5. extractionthe mixture extracted into EtOAc (3×10 mL)
  6. customThe combined organic layers were passed through a phase separation cartridge
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified via silica gel chromatography (0-100% EtOAc/isohexane)

Sources & evidence

ORD record
ord-b0e63136a3fa43bf863946388819bff1
Source dataset
uspto-grants-2013_12
Patent number
US08614206B2

Reaction notes

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