Phosphorus oxychloride → 3-[2-(3-Fluorophenyl)ethyl]-2-pyridinecarbonitrile

HRID 569203

Reaction equation

HRID 569203 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH2:8][CH2:9][C:10]2[C:11]([C:16]([NH:18]C(C)(C)C)=O)=[N:12][CH:13]=[CH:14][CH:15]=2)[CH:5]=[CH:6][CH:7]=1.P(Cl)(Cl)(Cl)=O>>[F:1][C:2]1[CH:3]=[C:4]([CH2:8][CH2:9][C:10]2[C:11]([C:16]#[N:18])=[N:12][CH:13]=[CH:14][CH:15]=2)[CH:5]=[CH:6][CH:7]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 147168133-[2-(3-fluorophenyl)ethyl]-N(1,1-dimethylethyl)-2-pyridine carboxamide

Product 1

HCID 147168143-[2-(3-Fluorophenyl)ethyl]-2-pyridinecarbonitrileYield 60%

Procedure

A solution of 3-[2-(3-fluorophenyl)ethyl]-N-(1,1-dimethylethyl)-2-pyridine carboxamide (36.4 g, 0.121 mole) in 123 mL (202.3 g, 1.32 mole) of phosphorous oxychloride is heated at 110° C. for 3.5 hours and stirred at ambient temperature an additional 15 hours. The reaction is quenched with ice and water and the pH of the solution is brought to 8 by the addition of a saturated aqueous solution of potassium carbonate. The product is extracted into ethyl acetate and the solution is concentrated to a residue. Following purification by silica gel chromatography and trituration with pentane, 16.2 g (0.072 mole) of product is obtained in 60% yield.

Workup

  1. customThe reaction is quenched with ice and water
  2. additionthe pH of the solution is brought to 8 by the addition of a saturated aqueous solution of potassium carbonate
  3. extractionThe product is extracted into ethyl acetate
  4. concentrationthe solution is concentrated to a residue
  5. custompurification by silica gel chromatography and trituration with pentane

Sources & evidence

ORD record
ord-a8a668ee0290443f87044b34d372f1fa
Source dataset
uspto-grants-1988_03
Patent number
US04731447

Linked notes

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