Hydrochloric Acid → 1-(2-Fluorobiphenyl-4-yl)cyclopropanecarboxylic acid

HRID 910881Notes

Reaction equation

Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:11]([OH:13])=[O:12])[CH2:10][CH2:9]2)=[CH:4][C:3]=1[F:14].[C:15]1(B(O)O)[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.C([O-])([O-])=O.[K+].[K+].Cl>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:14][C:3]1[CH:4]=[C:5]([C:8]2([C:11]([OH:13])=[O:12])[CH2:10][CH2:9]2)[CH:6]=[CH:7][C:2]=1[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

Participants

Conditions

Temperature: 130 °C

Procedure

800 mg (3.1 mmoles) of 4-bromo-3-fluorophenylcyclopropanecarboxylic acid and 650 mg (3.4 mmoles) of phenylboronic acid are suspended in 8 ml of a 2M K2CO3 aqueous solution. The mixture is added with tetrabutylammonium bromide (960 mg, 3 mmoles) and palladium(II) acetate (40 mg, 0.18 mmoles) and heated at 130° C. in a closed reactor for 30 minutes. After cooling at room temperature, the mixture is added with 2M HCl (25 ml) and extracted with ethyl acetate. The organic phase is washed with 1N HCl, then with brine, finally dried and concentrated under vacuum to give an oil (1.7 g), which is crystallized from isopropyl ether-hexane to afford the product as a white solid (0.2 g).

Workup

temperatureAfter cooling at room temperature
extractionextracted with ethyl acetate
washThe organic phase is washed with 1N HCl
dry with materialwith brine, finally dried
concentrationconcentrated under vacuum

Sources & evidence

ORD record: ord-99b73cb73f1b446e993f14784ccc6b71
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08022250B2

Reaction notes

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