3-Cyanopyridine → 1-Phenoxycarbonyl-4-(p-tolyl)-1,4-dihydropyridine

HRID 373123Notes

Reaction equation

HRID 373123 reaction equation
C([C:3]1[CH:4]=[N:5][CH:6]=[CH:7][CH:8]=1)#N.[C:9]1([CH3:17])[CH:14]=[CH:13][C:12]([Mg]Br)=[CH:11][CH:10]=1.S(C)C.Cl[C:22]([O:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)=[O:23].[NH4+].[Cl-]>CCOCC.[Cu]I.C1COCC1>[O:24]([C:22]([N:5]1[CH:4]=[CH:3][CH:8]([C:12]2[CH:13]=[CH:14][C:9]([CH3:17])=[CH:10][CH:11]=2)[CH:7]=[CH:6]1)=[O:23])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1

Participants

9

Reactant 5

HCID 793-CyanopyridineHCID 1068Dimethyl SulfideHCID 15891Phenyl chloroformateHCID 25517Ammonium ChlorideHCID 178418370HCID 178418370, compound

Product 1

HCID 198115101-Phenoxycarbonyl-4-(p-tolyl)-1,4-dihydropyridine

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 3283Diethyl EtherSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred mixture of 3-cyanopyridine (10 g, 96 mmol), CuI (914 mg, 4.8 mmol), p-tolylmagnesium bromide (100 mL of a 1M solution in Et2O, 100 mmol), THF (200 mL), and Me2S (100 mL) under N2 at 23° C. was added phenyl chloroformate (12.6 mL, 100 mmol) over a 30 min. period. After 2 h, aqueous NH4Cl (20%, 100 mL) and Et2O (100 mL) were added and the mixture was warmed to room temperature. The organic layer was washed sequentially with 1N HCl (50 mL), H2O (50 mL), a 1:1 mixture of 20% aqueous NH4Cl and conc. NH4OH (3×50 mL), and brine (50 mL) then dried (MgSO4). Concentration gave the crude 1-phenoxycarbonyl-4-(p-tolyl)-1,4-dihydropyridine as a tan solid. A portion (8 g) of this crude dihydropyridine was treated with S8 (810 mg) in decalin (25 mL) at reflux for 6 h. This reaction was cooled to rt, EtOAc (100 mL) and H2O (50 mL) were added and the resulting mixture was filtered through celite®. The organic layer was washed sequentially with 1N NaOH (30 mL), water and brine then dried over (K2CO3). Purification (flash chromatography, 20% EtOAc/hexanes) gave the titled compound as a tan solid.

Workup

  1. washThe organic layer was washed sequentially with 1N HCl (50 mL), H2O (50 mL)
  2. additiona 1:1 mixture of 20% aqueous NH4Cl and conc. NH4OH (3×50 mL), and brine (50 mL)
  3. dry with materialthen dried (MgSO4)
  4. concentrationConcentration

Sources & evidence

ORD record
ord-9878843a37b04eb9bbbddac620bb4608
Source dataset
uspto-grants-1992_11
Patent number
US05162325

Reaction notes

Loading…