Hydrochloric Acid → 2-(2-Chloro-5-fluoropyrimidin-4-yl)-benzo[b]thiophene-4-carboxylic acid

HRID 1986174Notes

Reaction equation

C([O-])([O-])=O.[Na+].[Na+].[C:7]([C:10]1[C:18]2[CH:17]=[C:16](B(O)O)[S:15][C:14]=2[CH:13]=[CH:12][CH:11]=1)([OH:9])=[O:8].[Cl:22][C:23]1[N:28]=[C:27](Cl)[C:26]([F:30])=[CH:25][N:24]=1.Cl>COCCOC.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:22][C:23]1[N:28]=[C:27]([C:16]2[S:15][C:14]3[CH:13]=[CH:12][CH:11]=[C:10]([C:7]([OH:9])=[O:8])[C:18]=3[CH:17]=2)[C:26]([F:30])=[CH:25][N:24]=1

Participants

Conditions

Temperature: 100 °C

Procedure

An aqueous 2N Na2CO3 solution (36 mL) is added dropwise to a stirred solution of (4-carboxybenzo[b]thiophen-2-yl)boronic acid (3.63 g, 18.8 mmol) and 2,4-dichloro-5-fluoropyrimidine (3.00 g, 18.0 mmol) in ethyleneglycol dimethyl ether (50 mL) at room temperature under nitrogen atmosphere. Upon the completion of addition, dichlorobis(triphenylphosphine)palladium(II) (0.22 g, 3% mol) is added in one portion, then the reaction mixture is heated at 100° C. overnight. The mixture is cooled to 10° C., then 37% HCl (10 mL) is added in portions to form a suspension. After filtration and washing with water, the solid is dried under vacuum. The dry solid is suspended in 30 mL of dichloromethane/ethanol (10:1), sonicated, filtered, and dried again to provide 2-(2-chloro-5-fluoropyrimidin-4-yl)-benzo[b]thiophene-4-carboxylic acid (2.95 g, 48% yield).

Workup

additionis added in one portion
temperatureThe mixture is cooled to 10° C.
customto form a suspension
filtrationAfter filtration
washwashing with water
customthe solid is dried under vacuum
customsonicated
filtrationfiltered
customdried again

Sources & evidence

ORD record: ord-1873dca97f9f4bb4a0023aa648dd7a9c
Source dataset: uspto-grants-2009_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07547691B2

Reaction notes

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