Chloroethane → 1-Ethyl-4-(3-cyano-4-fluorophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarbonitrile

HRID 218483

Reaction equation

HRID 218483 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([CH:10]2[C:15]([C:16]#[N:17])=[C:14]([CH3:18])[NH:13][C:12]([CH3:19])=[C:11]2[C:20]#[N:21])[CH:6]=[CH:7][C:8]=1[F:9])#[N:2].[H-].[Na+].C([O-])([O-])=O.[Cs+].[Cs+].[CH2:30](Cl)[CH3:31]>CN(C=O)C>[CH2:30]([N:13]1[C:14]([CH3:18])=[C:15]([C:16]#[N:17])[CH:10]([C:5]2[CH:6]=[CH:7][C:8]([F:9])=[C:3]([C:1]#[N:2])[CH:4]=2)[C:11]([C:20]#[N:21])=[C:12]1[CH3:19])[CH3:31]

Participants

6

Reactant 4

HCID 6337ChloroethaneHCID 10796Cesium carbonateHCID 24758Sodium hydrideHCID 597632464-(3-Cyano-4-fluorophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarbonitrile

Product 1

HCID 690425561-Ethyl-4-(3-cyano-4-fluorophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarbonitrile

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-(3-cyano-4-fluorophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarbonitrile (1 eq), from Synthetic Example 1, in DMF was added either NaH or Cs2CO3 (1.2 eq) at 0° C. After 30 min, ethyl chloride was introduced. The reaction mixture was stirred at rt overnight, and quenched with brine. The reaction mixture was extracted with EtOAc, washed with brine, and dried. Concentration followed by flash chromatography gave 1-ethyl-4-(3-cyano-4-fluorophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarbonitrile. 1H-NMR (400 MHz, DMSO-D6): δ=7.86 (dd, 1H), 7.69 (m, 1H), 7.55 (t, 1H), 4.57 (s, 1H), 3.12 (q, 2H), 2.1 (s, 6H), 1.4 (t, 3H) ppm.

Workup

  1. customquenched with brine
  2. extractionThe reaction mixture was extracted with EtOAc
  3. washwashed with brine
  4. customdried
  5. concentrationConcentration

Sources & evidence

ORD record
ord-69f6b9f24fd540fa94884e5aada17ec3
Source dataset
uspto-grants-2012_06
Patent number
US08198456B2

Linked notes

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