Diisopropylethylamine → 5-(5-Cyanopyridin-3-ylethynyl)-2-fluorobenzoic acid methyl ester

HRID 606900Notes

Reaction equation

HRID 606900 reaction equation
C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.C(N(C(C)C)CC)(C)C.[CH3:23][O:24][C:25](=[O:34])[C:26]1[CH:31]=[C:30](Br)[CH:29]=[CH:28][C:27]=1[F:33].[C:35]([C:37]1[CH:38]=[N:39][CH:40]=[C:41]([CH:44]=1)[C:42]#[N:43])#[CH:36]>O1CCOCC1.[Cu]I>[CH3:23][O:24][C:25](=[O:34])[C:26]1[CH:31]=[C:30]([C:36]#[C:35][C:37]2[CH:38]=[N:39][CH:40]=[C:41]([C:42]#[N:43])[CH:44]=2)[CH:29]=[CH:28][C:27]=1[F:33]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 21525435Methyl 5-bromo-2-fluorobenzoateHCID 224165635-Ethynylnicotinonitrile

Product 1

HCID 670476255-(5-Cyanopyridin-3-ylethynyl)-2-fluorobenzoic acid methyl esterYield 44.1%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 312751,4-DioxaneSolvent3×

Procedure

Sequentially add tri-tert-butylphosphine (88 mg, 0.437 mmol) in anhydrous 1,4-dioxane (1 mL), diisopropylethylamine (1.5 mL, 8.74 mmol), 5-bromo-2-fluorobenzoic acid methyl ester, (prepared as described in PREPARATION 42), (1.69 g, 7.28 mmol) and a solution of 5-ethynylnicotinonitrile, (prepared as described in PREPARATION 4), (0.93 g, 7.28 mmol) in anhydrous 1,4-dioxane (4 mL), to a stirring mixture of dichloro(benzonitrile)palladium (II) (84 mg, 0.218 mmol) and copper (I) iodide (28 mg, 0.146 mmol) in anhydrous 1,4-dioxane (1 mL) under nitrogen. Stir for 2 h and concentrate. Purify the residue twice by silica gel chromatography, eluting with 10:90 ethyl acetate:hexanes, to give the title compound as a white solid (0.9 g, 44%).

Workup

  1. concentrationconcentrate
  2. customPurify the residue twice by silica gel chromatography
  3. washeluting with 10:90 ethyl acetate

Sources & evidence

ORD record
ord-43d1c1dd35034439a698b92cd8d3b32f
Source dataset
uspto-grants-2011_03
Patent number
US07915424B2

Reaction notes

Loading…