1,2-Dimethoxyethane → 2-Fluoro-3-(4-methylpyridin-3-yl)benzonitrile

HRID 593736Notes

Reaction equation

HRID 593736 reaction equation
Br[C:2]1[C:3]([F:10])=[C:4]([CH:7]=[CH:8][CH:9]=1)[C:5]#[N:6].C(=O)([O-])[O-].[Na+].[Na+].[CH3:17][C:18]1[CH:23]=[CH:22][N:21]=[CH:20][C:19]=1B(O)O.COCCOC>C(Cl)Cl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O.CCO>[F:10][C:3]1[C:2]([C:19]2[CH:20]=[N:21][CH:22]=[CH:23][C:18]=2[CH3:17])=[CH:9][CH:8]=[CH:7][C:4]=1[C:5]#[N:6]

Participants

9

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 27612003-Bromo-2-fluorobenzonitrileHCID 27627114-Methylpyridine-3-Boronic Acid

Product 1

HCID 867303982-Fluoro-3-(4-methylpyridin-3-yl)benzonitrileYield 73.3%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A reaction flask was charged with tetrakis(triphenylphosphine)palladium(0) (1.040 g, 0.900 mmol), 3-bromo-2-fluorobenzonitrile (3.6 g, 18.00 mmol), sodium carbonate (7.63 g, 72.0 mmol), and 4-methylpyridin-3-ylboronic acid (2.59 g, 18.90 mmol). The mixture was stirred at room temperature for 10 min under N2, then DME (67.2 mL), EtOH (33.6 mL), and water (33.6 mL) were added sequentially. The resultant mixture was heated at 90° C. overnight. After 17 hr, the reaction mixture was allowed to cool to room temperature. The reaction was quenched with water. The reaction mixture was diluted with EtOAc. The layers were separated and the aqueous phase was extracted with EtOAc (3×). The organic phases were combined, dried over Na2SO4, filtered, and concentrated to afford a brown residue. The crude material was dissolved in a minimal amount of CH2Cl2 to be chromatographed. Purification of the crude material by silica gel chromatography using an ISCO machine (120 g column, 85 mL/min, 0-70% EtOAc in hexanes over 25 min, tr=15 min) gave the title compound (2.80 g, 13.19 mmol, 73.3% yield) as a purple residue. ESI MS (M+H)+=213.1. HPLC Peak tr=1.01 minutes. Purity >99%. HPLC Conditions: C.

Workup

  1. waitAfter 17 hr
  2. temperatureto cool to room temperature
  3. customThe reaction was quenched with water
  4. additionThe reaction mixture was diluted with EtOAc
  5. customThe layers were separated
  6. extractionthe aqueous phase was extracted with EtOAc (3×)
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto afford a brown residue
  11. customto be chromatographed
  12. customPurification of the crude material by silica gel chromatography
  13. customan ISCO machine (120 g column, 85 mL/min, 0-70% EtOAc in hexanes over 25 min, tr=15 min)

Sources & evidence

ORD record
ord-1429e4977a094603815f6d3e9ca859e8
Source dataset
uspto-grants-2016_01
Patent number
US09242967B2

Reaction notes

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