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

HRID 1799205

Reaction equation

HRID 1799205 reaction equation
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

Participants

8

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 27343694-Methoxycarbonylphenylboronic acidHCID 66724952(4R)-4-(3-bromo-4-chlorophenyl)pyrrolidin-2-one

Product 1

HCID 667251414-[5-((3R)-5-oxopyrrolidin-3-yl)-2-chlorophenyl]benzoic acid

Reagents, catalysts & solvents 4

HCID 74236Tetrabutylammonium BromideCatalystHCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

(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)+.

Workup

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

Sources & evidence

ORD record
ord-836e300eda1443bc8729141dc580c4a6
Source dataset
uspto-grants-2013_01
Patent number
US08344028B2

Linked notes

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