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

HRID 1799205

반응식

HRID 1799205 반응식
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

참가 물질

8

반응물 3

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

생성물 1

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

시약·촉매·용매 4

HCID 74236Tetrabutylammonium Bromide촉매HCID 167845palladium(II) acetate촉매HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

반응 조건

온도
90 °C

실험 절차

(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)+.

후처리

  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

출처 및 근거

ORD 기록
ord-836e300eda1443bc8729141dc580c4a6
출처 데이터셋
uspto-grants-2013_01
특허 번호
US08344028B2

연결된 노트

불러오는 중…