Potassium Phosphate, Tribasic → 4-[5-((3R)-5-oxopyrrolidin-3-yl)-2-chlorophenyl]benzoic acid

HRID 1799205

Reaktionsgleichung

Br[C:2]1[CH:3]=[C:4]([C@@H:9]2[CH2:13][NH:12][C:11](=[O:14])[CH2:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8].C[O:16][C:17]([C:19]1[CH:24]=[CH:23][C:22](B(O)O)=[CH:21][CH:20]=1)=[O:18].P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[O:14]=[C:11]1[NH:12][CH2:13][C@@H:9]([C:4]2[CH:5]=[CH:6][C:7]([Cl:8])=[C:2]([C:22]3[CH:23]=[CH:24][C:19]([C:17]([OH:18])=[O:16])=[CH:20][CH:21]=3)[CH:3]=2)[CH2:10]1

Komponenten

Reaktionsbedingungen

Temperatur: 90 °C

Versuchsvorschrift

(4R)-4-(3-Bromo-4-chlorophenyl)pyrrolidin-2-one (0.5 g, 0.55 mmol) and 4-methoxycarbonylphenyl boronic acid (0.144 g, 0.55 mmol) were mixed in DMF (2 mL). The mixture was degassed by alternately applying a vacuum and flushing with nitrogen gas. Palladium acetate (0.025 g, 0.11 mmol) and tetrabutylammonium bromide (0.053 g, 0.165 mmol) were added followed by potassium phosphate (0.35 g, 1.65 mmol). The mixture was stirred overnight at 90° C. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (50 mL), washed with 10% aqueous HCl solution then brine, and concentrated in vacuo to provide 4-[5-((3R)-5-oxopyrrolidin-3-yl)-2-chlorophenyl]benzoic acid. 4-[5-((3R)-5-Oxopyrrolidin-3-yl)-2-chlorophenyl]benzoic acid was then treated with HCl as described for the preparation of (3R)-4-amino-3-(3-bromo-4-chlorophenyl)butanoic acid hydrochloride to provide the title compound (24). MS (ESI) m/z 334.07 (M+H)+.

Aufarbeitung

customThe mixture was degassed
customflushing with nitrogen gas
temperatureThe reaction mixture was cooled to room temperature
washwashed with 10% aqueous HCl solution
concentrationbrine, and concentrated in vacuo

Quellen und Nachweise

ORD-Eintrag: ord-836e300eda1443bc8729141dc580c4a6
Quelldatensatz: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patentnummer: US08344028B2

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