Sodium Carbonate → 4-(5-Ethoxy-2-fluoro-phenyl)-3,6-dimethyl-pyridine-2-carbonitrile

HRID 2207664Notes

Reaction equation

HRID 2207664 reaction equation
Br[C:2]1[CH:7]=[C:6]([CH3:8])[N:5]=[C:4]([C:9]#[N:10])[C:3]=1[CH3:11].[CH2:12]([O:14][C:15]1[CH:16]=[CH:17][C:18]([F:24])=[C:19](B(O)O)[CH:20]=1)[CH3:13].C(=O)([O-])[O-].[Na+].[Na+]>CC#N.O.C1(C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)[Pd][P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH2:12]([O:14][C:15]1[CH:16]=[CH:17][C:18]([F:24])=[C:19]([C:2]2[CH:7]=[C:6]([CH3:8])[N:5]=[C:4]([C:9]#[N:10])[C:3]=2[CH3:11])[CH:20]=1)[CH3:13]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 162174685-Ethoxy-2-fluorophenylboronic Acid (contains varying amounts of Anhydride)HCID 896490174-Bromo-3,6-dimethyl-pyridine-2-carbonitrile

Product 1

HCID 896488144-(5-Ethoxy-2-fluoro-phenyl)-3,6-dimethyl-pyridine-2-carbonitrileYield 97.3%

Reagents, catalysts & solvents 3

HCID 178419050HCID 178419050, compoundCatalystHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 4-bromo-3,6-dimethyl-pyridine-2-carbonitrile (which may be prepared as described in Description 137) (3.82 g, 18.099 mmol) in MeCN (45 mL) and water (5 mL) in a Smith microwave vessel was added (5-ethoxy-2-fluoro-phenyl)boronic acid (3.6627 g, 19.909 mmol), bis(triphenylphosphine)palladium (II) dichloride (0.3811 g, 0.5430 mmol) and sodium carbonate (3.8367 g, 36.198 mmol). The reaction vessel was sealed and purged with nitrogen. The reaction mixture was heated by microwave at 100° C. for 25 min. The reaction mixture was treated with water and was extracted with DCM twice and the organic layers were collected by passing down a PhaseSep cartridge The solvent was removed by evaporation and the residue was purified by silica gel chromatography (100 g SiO2) eluting with ethyl acetate in iso-hexane (10-60%). Evaporation of desired fractions gave 4-(5-ethoxy-2-fluoro-phenyl)-3,6-dimethyl-pyridine-2-carbonitrile (D138) (4.76 g, 17.61 mmol, 97.3% yield);

Workup

  1. customThe reaction vessel was sealed
  2. custompurged with nitrogen
  3. additionThe reaction mixture was treated with water
  4. extractionwas extracted with DCM twice
  5. customthe organic layers were collected
  6. customwas removed by evaporation
  7. customthe residue was purified by silica gel chromatography (100 g SiO2)
  8. washeluting with ethyl acetate in iso-hexane (10-60%)
  9. customEvaporation of desired fractions

Sources & evidence

ORD record
ord-ef818985bb3a4184baf9b5558420c225
Source dataset
uspto-grants-2016_06
Patent number
US09376436B2

Reaction notes

Loading…