Triethylamine → 2-Fluoro-5-(5-methoxypyridin-3-ylethynyl)-benzoic acid

HRID 606939Notes

Reaction equation

HRID 606939 reaction equation
[C:1]([C:3]1[CH:4]=[N:5][CH:6]=[C:7]([O:9][CH3:10])[CH:8]=1)#[CH:2].[F:11][C:12]1[CH:20]=[CH:19][C:18](I)=[CH:17][C:13]=1[C:14]([OH:16])=[O:15].C(N(CC)CC)C>C1(C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)[Pd][P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[F:11][C:12]1[CH:20]=[CH:19][C:18]([C:2]#[C:1][C:3]2[CH:4]=[N:5][CH:6]=[C:7]([O:9][CH3:10])[CH:8]=2)=[CH:17][C:13]=1[C:14]([OH:16])=[O:15]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 27789252-Fluoro-5-iodobenzoic acidHCID 210973493-Ethynyl-5-methoxypyridine

Product 1

HCID 670477592-Fluoro-5-(5-methoxypyridin-3-ylethynyl)-benzoic acidYield 54.4%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178419050HCID 178419050, compoundCatalyst

Procedure

Add bis(triphenylphosphine)palladium (II) dichloride (70 mg, 0.10 mmol), copper (I) iodide (38 mg, 0.20 mmol), and 3-ethynyl-5-methoxypyridine, (prepared as described in PREPARATION 10), (400 mg, 3.0 mmol) to a solution of 2-fluoro-5-iodobenzoic acid (0.53 g, 2.0 mmol) in triethylamine (4.2 mL, 30.0 mmol) and stir at room temperature for 1 h. Heat at 50° C. for 18 h. Cool to room temperature and concentrate. Purify by silica gel chromatography, eluting with 100:0 to 60:40 ethyl acetate:methanol. Triturate the resulting solid with 3:1 hexanes:methanol to give the title compound as an off-white solid (295 mg, 54%).

Workup

  1. temperatureHeat at 50° C. for 18 h
  2. temperatureCool to room temperature
  3. concentrationconcentrate
  4. customPurify by silica gel chromatography
  5. washeluting with 100:0 to 60:40 ethyl acetate
  6. customTriturate the resulting solid with 3:1 hexanes

Sources & evidence

ORD record
ord-cf46995eddec4883b9ee02bc24a1c525
Source dataset
uspto-grants-2011_03
Patent number
US07915424B2

Reaction notes

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