4-[(2-Bromo-2,2-difluoroacetyl)-(2-iodophenyl)amino]piperidine-1-carboxylic acid tert-butyl ester → 4-(3,3-Difluoro-2-oxo-2,3-dihydroindol-1-YL)-piperidine-1-carboxylic acid tert-butyl ester

HRID 552132Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 552132
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]([C:22](=[O:27])[C:23](Br)([F:25])[F:24])[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2I)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]>CS(C)=O.[Cu]>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[C:15]3[C:20](=[CH:19][CH:18]=[CH:17][CH:16]=3)[C:23]([F:25])([F:24])[C:22]2=[O:27])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Komponenten

4

Edukt 1

HCID 671716824-[(2-Bromo-2,2-difluoroacetyl)-(2-iodophenyl)amino]piperidine-1-carboxylic acid tert-butyl ester

Produkt 1

HCID 866171214-(3,3-Difluoro-2-oxo-2,3-dihydroindol-1-YL)-piperidine-1-carboxylic acid tert-butyl esterAusbeute 93 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 23978CopperKatalysatorHCID 679Dimethyl SulfoxideLösungsmittel

Reaktionsbedingungen

Temperatur
70 °C

Versuchsvorschrift

A mixture of 4-[(2-bromo-2,2-difluoroacetyl)-(2-iodophenyl)amino]-piperidine-1-carboxylic acid tert-butyl ester (1.670 g, 2.98 mmol) and copper (bronze, 0.480 g, 7.55 mmol) in DMSO (15 mL) was heated at 70° C. overnight. The reaction mixture was quenched with water at 0° C. and then extracted with ethyl acetate. The combined organic phase was washed with water and brine, dried over anhydrous Na2SO4 and concentrated. Purification of the residue by flash chromatography to afford the title compound in 93% yield (0.976 g). 1H NMR (300 MHz, CDCl3) δ 7.52-7.40 (m, 2H), 7.12 (t, J=7.5 Hz, 1H), 7.00 (t, J=8.1 Hz, 1H), 4.28-4.13 (m, 3H), 2.77 (t, J=12.9 Hz, 2H), 2.32-2.18 (m, 2H), 1.73 (d, J=12.9 Hz, 2H), 1.45 (s, 9H). 13C NMR (75 MHz, CDCl3) δ 165.5, 165.0, 164.6, 154.5, 142.6, 142.5, 142.4, 133.4, 125.0, 123.6, 120.6, 120.3, 120.0, 113.6, 110.9, 110.3, 107.0, 80.0, 77.5, 77.0, 76.6, 51.0, 43.2, 28.3, 27.9. MS (ES+) m/z 375.3 (M+Na).

Aufarbeitung

  1. customThe reaction mixture was quenched with water at 0° C.
  2. extractionextracted with ethyl acetate
  3. washThe combined organic phase was washed with water and brine
  4. dry with materialdried over anhydrous Na2SO4
  5. concentrationconcentrated
  6. customPurification of the residue by flash chromatography

Quellen und Nachweise

ORD-Eintrag
ord-7b90b1988f5e4fa489807c0bb9fe650c
Quelldatensatz
uspto-grants-2011_05
Patentnummer
US07951805B2

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