1,4-Dioxane → 1-(6-Azetidin-1-ylpyridin-3-yl)cyclopropanecarbonitrile

HRID 557970Notes

Reaction equation

HRID 557970 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([C:8]2([C:11]#[N:12])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.O1CCOCC1.Cl.[NH:20]1[CH2:23][CH2:22][CH2:21]1.CC(C)([O-])C.[Na+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[N:20]1([C:2]2[N:7]=[CH:6][C:5]([C:8]3([C:11]#[N:12])[CH2:10][CH2:9]3)=[CH:4][CH:3]=2)[CH2:23][CH2:22][CH2:21]1

Participants

6

Reactant 4

HCID 312751,4-DioxaneHCID 12308726Azetidine hydrochlorideHCID 221593571-(6-Chloropyridin-3-yl)cyclopropane-1-carbonitrileHCID 23676156Sodium t-butoxide

Product 1

HCID 666627061-(6-Azetidin-1-ylpyridin-3-yl)cyclopropanecarbonitrile

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Procedure

To a solution of 1-(6-chloropyridin-3-yl)cyclopropanecarbonitrile (200.0 mg, 0.001120 mol) in 1,4-dioxane (8.00 mL, 0.102 mol) at rt were added azetidine hydrochloride (128.3 mg, 0.001344 mol), palladium acetate (25.2 mg, 0.000112 mol), and sodium tert-butoxide (288 mg, 0.00291 mol). The reaction mixture was degassed and then microwave irradiated at 150° C. for 40 min. The reaction mixture was quenched with water and extracted with ethyl acetate and dichloromethane. The crude product was purified by combiflash. LCMS: m/z 200.2 (M+H)+.

Workup

  1. customThe reaction mixture was degassed
  2. custommicrowave irradiated at 150° C. for 40 min
  3. customThe reaction mixture was quenched with water
  4. extractionextracted with ethyl acetate and dichloromethane
  5. customThe crude product was purified by combiflash

Sources & evidence

ORD record
ord-09e51060174a49aeafe89b51b7479f76
Source dataset
uspto-grants-2011_11
Patent number
US08058288B2

Reaction notes

Loading…