Triethylamine → (4-Chloro-2-{[2-fluoro-5-(methylsulfonyl)phenyl]ethynyl}phenoxy)acetic acid

HRID 2390342Notes

Reaction equation

C([O:5][C:6](=[O:18])[CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([Cl:15])=[CH:11][C:10]=1[C:16]#[CH:17])(C)(C)C.[F:19][C:20]1[CH:25]=[CH:24][C:23]([S:26]([CH3:29])(=[O:28])=[O:27])=[CH:22][C:21]=1I.C(N(CC)CC)C>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C1COCC1>[Cl:15][C:12]1[CH:13]=[CH:14][C:9]([O:8][CH2:7][C:6]([OH:5])=[O:18])=[C:10]([C:16]#[C:17][C:21]2[CH:22]=[C:23]([S:26]([CH3:29])(=[O:27])=[O:28])[CH:24]=[CH:25][C:20]=2[F:19])[CH:11]=1

Participants

Conditions

Temperature: 60 °C

Procedure

A mixture of (4-chloro-2-ethynyl-phenoxy)-acetic acid tert-butyl ester (Intermediate 3, 164 mg; 0.61 mmol), 1-fluoro-2-iodo-4-(methylsulfonyl)benzene (Intermediate 58, 184 mg; 0.61 mmol), 1,1′-bis(diphenylphosphino)ferrocenedichloro palladium(ii) (27 mg; 0.04 mmol) and cuprous iodide (7 mg; 0.04 mmol) was degassed during two minutes under nitrogen then anhydrous THF (3 mL) and triethylamine (170 μL; 1.23 mmol) were added and reaction mixture was stirred at 60° C. for 60 hours. The solvent was evaporated and the residue was treated with an HCl solution (4 N in dioxane, 3.7 mL). After stirring for 16 hours, the solvents were removed under vacuum and the crude product purified by preparative HPLC. The title compound was obtained as a brown solid.

Workup

customwas degassed during two minutes under nitrogen
customreaction mixture
customThe solvent was evaporated
additionthe residue was treated with an HCl solution (4 N in dioxane, 3.7 mL)
stirringAfter stirring for 16 hours
customthe solvents were removed under vacuum
customthe crude product purified by preparative HPLC

Sources & evidence

ORD record: ord-0312b81193204295a6ce15301618c40f
Source dataset: uspto-grants-2012_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08273769B2

Reaction notes

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