N-methyl-2-pyrrolidone → HCID 58495633, compound

HRID 1190976Notes

Reaction equation

HRID 1190976 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([O:8][CH:9]2[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]2)=[CH:4][CH:3]=1.[Cu][C:16]#[N:17].CN1C(=O)CCC1>[NH4+].[OH-]>[CH:9]1([O:8][C:5]2[CH:4]=[CH:3][C:2]([C:16]#[N:17])=[N:7][CH:6]=2)[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1

Participants

5

Reactant 3

HCID 13387N-methyl-2-pyrrolidoneHCID 58495607HCID 58495607, compoundHCID 178418546HCID 178418546, compound2×

Product 1

HCID 58495633HCID 58495633, compoundYield 57.1%

Reagents, catalysts & solvents 1

HCID 14923Ammonium HydroxideSolvent

Conditions

Temperature
180 °C

Procedure

Under a nitrogen atmosphere, add 6-chloro-3-cyclohexyloxy-pyridine (1.5 g, 7.1 mmol) and copper(I) cyanide (1.89 g, 21 mmol) to NMP (15 mL). Heat the mixture at 180° C. overnight. Cool the mixture to room temperature and add copper(I) cyanide (0.63 g, 7.1 mmol). Heat the mixture at 180° C. for 6 h. Cool the mixture to room temperature, dilute with 5N aqueous NH4OH and extract with DCM. Separate the layers and extract the aqueous phase with additional DCM. Wash the combined organic extracts with water and brine. Dry the organic phase over Na2SO4, filter, and concentrate in vacuo. Purify the residue by chromatography on silica gel (500 g) eluting with hexane/EtOAc (20:1) to obtain the desired intermediate (820 mg, 57%). MS (ES+) m/z: 203 (M+H)+.

Workup

  1. temperatureCool the mixture to room temperature
  2. temperatureHeat the mixture at 180° C. for 6 h
  3. temperatureCool the mixture to room temperature
  4. extractionextract with DCM
  5. customSeparate the layers
  6. extractionextract the aqueous phase with additional DCM
  7. washWash the combined organic extracts with water and brine
  8. dry with materialDry the organic phase over Na2SO4
  9. filtrationfilter
  10. concentrationconcentrate in vacuo
  11. customPurify the residue by chromatography on silica gel (500 g)
  12. washeluting with hexane/EtOAc (20:1)

Sources & evidence

ORD record
ord-f874173796d8498daab7e1f6308d8e9d
Source dataset
uspto-grants-2014_03
Patent number
US08680091B2

Reaction notes

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