Potassium Hydroxide → rac-(2S,3S,4S)-2-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-4-(2,2-dimethyl-propyl)-pyrrolidine-3-carbonitrile

HRID 909009Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 909009
[Cl:1][C:2]1[C:3]([F:11])=[C:4](/[CH:8]=[N:9]/[CH3:10])[CH:5]=[CH:6][CH:7]=1.[Cl:12][C:13]1[CH:18]=[CH:17][C:16](/[C:19](=[CH:22]/[CH2:23][C:24]([CH3:27])([CH3:26])[CH3:25])/[C:20]#[N:21])=[C:15]([F:28])[CH:14]=1.[OH-].[K+]>CS(C)=O.O>[Cl:1][C:2]1[C:3]([F:11])=[C:4]([CH:8]2[C:19]([C:16]3[CH:17]=[CH:18][C:13]([Cl:12])=[CH:14][C:15]=3[F:28])([C:20]#[N:21])[CH:22]([CH2:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH2:10][NH:9]2)[CH:5]=[CH:6][CH:7]=1.[Cl:1][C:2]1[C:3]([F:11])=[C:4]([CH:8]2[NH:9][CH2:10][C:19]([C:16]3[CH:17]=[CH:18][C:13]([Cl:12])=[CH:14][C:15]=3[F:28])([C:20]#[N:21])[CH:22]2[CH2:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH:5]=[CH:6][CH:7]=1

Komponenten

7

Edukt 3

HCID 14797Potassium HydroxideHCID 58222872(Z)-2-(4-chloro-2-fluoro-phenyl)-5,5-dimethyl-hex-2-enenitrileHCID 178482759HCID 178482759, Verbindung

Produkt 2

HCID 67095372rac-(2S,3S,4S)-2-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-4-(2,2-dimethyl-propyl)-pyrrolidine-3-carbonitrileAusbeute 20,3 %HCID 77225006rac (3S,4S,5S)-5-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-4-(2,2-dimethyl-propyl)pyrrolidine-3-carbonitrileAusbeute 15,6 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 679Dimethyl SulfoxideLösungsmittelHCID 962WaterLösungsmittel

Versuchsvorschrift

To a solution of [1-(3-chloro-2-fluoro-phenyl)-meth-(E)-ylidene]-methyl-amine (1.72 g, 10.00 mmol) and (Z)-2-(4-chloro-2-fluoro-phenyl)-5,5-dimethyl-hex-2-enenitrile (2.52 g, 10.00 mmol) in DMSO (10 mL) was added KOH powder (1.12 g, 20.00 mmol) in one portion. The mixture was stirred at rt overnight. The reaction mixture was diluted with water and extracted with EtOAc three times (3×50 mL). The combined organic layers were washed with water and brine and dried over Na2SO4, and concentrated. The residue was purified by flash column (SiO2, 1%-15% of EtOAc in hexanes) after concentration to give rac-(2S,3S,4S)-2-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-4-(2,2-dimethyl-propyl)-pyrrolidine-3-carbonitrile (0.86 g, 20.3%; HRMS (ES+) m/z Calcd for C22H22Cl2F2N2+H [(M+H)+]: 423.1201, found: 423.1199) and rac (3S,4S,5S)-5-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-4-(2,2-dimethyl-propyl)pyrrolidine-3-carbonitrile (0.66 g, 15.6%); HRMS (ES+) m/z Calcd for C22H22Cl2F2N2+H [(M+H)+]: 423.1201. found: 423.1202.

Aufarbeitung

  1. extractionextracted with EtOAc three times (3×50 mL)
  2. washThe combined organic layers were washed with water and brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. customThe residue was purified by flash column (SiO2, 1%-15% of EtOAc in hexanes)
  6. concentrationafter concentration

Quellen und Nachweise

ORD-Eintrag
ord-375e7d6bfc444976826e8d30978b8cd1
Quelldatensatz
uspto-grants-2011_09
Patentnummer
US08017607B2

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