Dimethylformamide → 3-{5-[(1R)-2-Amino-1-(carboxymethyl)ethyl]-2-chlorophenyl}benzoic acid hydrochloride

HRID 1799207

반응식

HRID 1799207 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:20]=[C:21](B(O)O)[CH:22]=[CH:23][CH:24]=1)=[O:18].CN(C=[O:32])C.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[ClH:8].[NH2:12][CH2:13][C@@H:9]([C:4]1[CH:5]=[CH:6][C:7]([Cl:8])=[C:2]([C:23]2[CH:24]=[C:19]([CH:20]=[CH:21][CH:22]=2)[C:17]([OH:18])=[O:16])[CH:3]=1)[CH2:10][C:11]([OH:14])=[O:32]

참가 물질

8

반응물 4

HCID 6228DimethylformamideHCID 62657Potassium Phosphate, TribasicHCID 27347143-(Methoxycarbonyl)benzeneboronic acidHCID 66724952(4R)-4-(3-bromo-4-chlorophenyl)pyrrolidin-2-one

생성물 1

HCID 667250703-{5-[(1R)-2-Amino-1-(carboxymethyl)ethyl]-2-chlorophenyl}benzoic acid hydrochloride

시약·촉매·용매 3

HCID 74236Tetrabutylammonium Bromide촉매HCID 167845palladium(II) acetate촉매HCID 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 3-methoxycarbonylphenyl boronic acid (0.144 g, 0.55 mmol) were mixed with DMF (2 mL). The mixture was degassed by alternately applying a vacuum and flushing with nitrogen. 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., then cooled to room temperature, diluted with ethyl acetate (30 mL), washed with a 10% aqueous HCl solution then brine, and concentrated in vacuo. The product, 3-[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 (25). 1H-NMR (400 MHz, CD3OD): δ8.03-8.06 m, 2H), 7.65-7.68 (m, 2H), 7.55-7.57 (m, 1H), 7.33-7.37 (m, 2H), 3.42-3.49 (m, 1H), 3.2-3.26 (m, 2H), 2.77-2.83 (dd, J=16.8, 6.4 Hz, 1H), 2.63-2.69 (dd, J=16.4, 7.6 Hz, 1H); MS (ESI) m/z 333.98 (M+H)+.

후처리

  1. customThe mixture was degassed
  2. customflushing with nitrogen
  3. temperaturecooled to room temperature
  4. washwashed with a 10% aqueous HCl solution
  5. concentrationbrine, and concentrated in vacuo
  6. additionThe product, 3-[5-((3R)-5-oxopyrrolidin-3-yl)-2-chlorophenyl]benzoic acid, was then treated with HCl
  7. customas described for the preparation of (3R)-4-amino-3-(3-bromo-4-chlorophenyl)butanoic acid hydrochloride

출처 및 근거

ORD 기록
ord-a8c954e7ca1545b491053e4d53ea3417
출처 데이터셋
uspto-grants-2013_01
특허 번호
US08344028B2

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