Water → 3-Fluoro-5-[(4-fluorophenyl)methyl]-2-pyridinecarbonitrile

HRID 2364525Notes

Reaction equation

HRID 2364525 reaction equation
[F:1][C:2]1[C:3]([C:9]#[N:10])=[N:4][CH:5]=[C:6](I)[CH:7]=1.[Cl-].[F:12][C:13]1[CH:20]=[CH:19][C:16]([CH2:17][Zn+])=[CH:15][CH:14]=1.O.C(OCC)(=O)C>C1COCC1.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>[F:1][C:2]1[C:3]([C:9]#[N:10])=[N:4][CH:5]=[C:6]([CH2:17][C:16]2[CH:19]=[CH:20][C:13]([F:12])=[CH:14][CH:15]=2)[CH:7]=1

Participants

7

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 210758683-Fluoro-5-iodopicolinonitrileHCID 178505764HCID 178505764, compound

Product 1

HCID 694815193-Fluoro-5-[(4-fluorophenyl)methyl]-2-pyridinecarbonitrileYield 75%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-fluoro-5-iodo-2-pyridinecarbonitrile(2.31 g, 9.3 mmol) in THF (100 mL) was added 4-fluorobenzyl zinc chloride (27.9 mL, 0.5 M in THF, 14.0 mmol) followed by Pd(PPh3)4 (538 mg, 0.47 mmol). The resultant solution was heated at 75° C. (bath temperature) for 3 hours. After cooling to room temperature, water and ethyl acetate were added. The layers were separated and the organic layer was washed with brine. The aqueous layer was acidified with 1 N HCl until it cleared and extracted with ethyl acetate. The combined organics were dried over sodium sulphate. Filtration and concentration followed by purification by silica gel chromatography provided 3-fluoro-5-[(4-fluorophenyl)methyl]-2-pyridinecarbonitrile (1.6 g, 75%) as a yellow solid. 1H NMR (400 MHz, CDCl3) δ 8.40 (s, 1 H), 7.28 (d, J=8.8 Hz, 1 H), 7.12 (dd, J=8.4, 5.2 Hz, 2 H), 7.03 (t, J=8.4 Hz, 2 H), 4.04 (s, 2 H). MS m/z 231 (M+1).

Workup

  1. customThe layers were separated
  2. washthe organic layer was washed with brine
  3. extractionextracted with ethyl acetate
  4. dry with materialThe combined organics were dried over sodium sulphate
  5. filtrationFiltration and concentration
  6. customfollowed by purification by silica gel chromatography

Sources & evidence

ORD record
ord-3e717676fa2f47f39c4df560e48c9800
Source dataset
uspto-grants-2014_04
Patent number
US08691991B2

Reaction notes

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