Dimethylformamide → 5-Fluoropyridine-3-carbonitrile

HRID 717546Notes

Reaction equation

HRID 717546 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([F:8])[CH:7]=1.[CH3:9][N:10](C)C=O>[C-]#N.[C-]#N.[Zn+2].C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:8][C:6]1[CH:5]=[N:4][CH:3]=[C:2]([CH:7]=1)[C:9]#[N:10]

Participants

6

Reactant 2

HCID 6228DimethylformamideHCID 8202063-Bromo-5-fluoropyridine

Product 1

HCID 224634715-Fluoropyridine-3-carbonitrile

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
130 °C

Procedure

Zn(CN)2 (2.45 g, 0.020 mol) and 1,1′-bis(diphenylphosphino)ferrocene (0.045 g, 0.0008 mol) were added to a solution of 3-bromo-5-fluoro pyridine (3.5 g, 0.0198 mol) in dimethylformamide. The reaction vessel was purged with argon for 10 min. Next, Pd2(dba)3 (0.04 g, 0.000043 mol) was added and the reaction vessel was purged with argon for another 5 min. The reaction mixture heated to 130° C. for 40 min under microwave irradiation. The reaction mixture was cooled to RT, diluted with water (100 mL) and extracted with ethyl acetate (3×100 mL). The combined organic layers were washed with a saturated aqueous sodium chloride solution (2×100 mL) and dried over sodium sulphate. The combined organic layers were then concentrated under vacuum to get crude product, which was purified by silica gel column chromatography to afford 5-fluoronicotinonitrile. 1H NMR (400 MHz, CDCl3) δ 8.72 (s, 1H), 8.71-8.70 (d, J=4 Hz, 1H), 7.70-7.76 (d, J=4 Hz, 1H).

Workup

  1. customThe reaction vessel was purged with argon for 10 min
  2. customthe reaction vessel was purged with argon for another 5 min
  3. temperatureThe reaction mixture was cooled to RT
  4. additiondiluted with water (100 mL)
  5. extractionextracted with ethyl acetate (3×100 mL)
  6. washThe combined organic layers were washed with a saturated aqueous sodium chloride solution (2×100 mL)
  7. dry with materialdried over sodium sulphate
  8. concentrationThe combined organic layers were then concentrated under vacuum
  9. customto get crude product, which
  10. customwas purified by silica gel column chromatography

Sources & evidence

ORD record
ord-b704d110ee5e42bdade92d8551570d9f
Source dataset
uspto-grants-2015_11
Patent number
US09193724B2

Reaction notes

Loading…