Acetone Cyanohydrin → 4-[(R)-3-Cyano-3-(3,5-dichloro-phenyl)-4,4,4-trifluoro-butyryl]-2-methyl-benzoic acid tert-butyl ester

HRID 589636

Reaktionsgleichung

Reaktionsgleichung von HRID 589636
[C-]#N.[K+].[Cl-].[Cs+].CC(C)(O)[C:8]#[N:9].[C:12]([O:16][C:17](=[O:41])[C:18]1[CH:23]=[CH:22][C:21]([C:24](=[O:39])/[CH:25]=[C:26](\[C:31]2[CH:36]=[C:35]([Cl:37])[CH:34]=[C:33]([Cl:38])[CH:32]=2)/[C:27]([F:30])([F:29])[F:28])=[CH:20][C:19]=1[CH3:40])([CH3:15])([CH3:14])[CH3:13]>C1(C)C=CC=CC=1.O>[C:12]([O:16][C:17](=[O:41])[C:18]1[CH:23]=[CH:22][C:21]([C:24](=[O:39])[CH2:25][C@:26]([C:8]#[N:9])([C:31]2[CH:36]=[C:35]([Cl:37])[CH:34]=[C:33]([Cl:38])[CH:32]=2)[C:27]([F:28])([F:30])[F:29])=[CH:20][C:19]=1[CH3:40])([CH3:15])([CH3:14])[CH3:13]

Komponenten

7

Edukt 4

HCID 6406Acetone CyanohydrinHCID 9032Potassium CyanideHCID 24293Cesium ChlorideHCID 866959924-[(E)-3-(3,5-Dichloro-phenyl)-4,4,4-trifluoro-but-2-enoyl]-2-methyl-benzoic acid tert-butyl ester

Produkt 1

HCID 547617414-[(R)-3-Cyano-3-(3,5-dichloro-phenyl)-4,4,4-trifluoro-butyryl]-2-methyl-benzoic acid tert-butyl esterAusbeute 79,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

Potassium cyanide (0.0377 g, 0.578 mmol), cesium chloride (0.0086 g, 0.051 mmol) and acetone cyanohydrin (0.142 ml, 1.55 mmol) were added to a solution of 4-[(E)-3-(3,5-dichloro-phenyl)-4,4,4-trifluoro-but-2-enoyl]-2-methyl-benzoic acid tert-butyl ester (0.250 g, 0.512 mmol) in toluene (5.0 ml). To this vigorously stirred suspension was added antracen-9-yl-methyl quininium chloride (0.071 g, 0.129 mmol). The reaction mixture was stirred at 90° C. for 18 hours. At this time water was added and the reaction mixture was extracted with dichloromethane (3×). The crude product was purified by flash chromatography (0% to 5% ethyl acetate in cyclohexane) to afford 4-[(R)-3-Cyano-3-(3,5-dichloro-phenyl)-4,4,4-trifluoro-butyryl]-2-methyl-benzoic acid tert-butyl ester (0.197 g, 79%) as a white foam. Chiral HPLC analysis (Chiralpack IB, Heptane:2-propanol=90:10, 1 ml/min, retention time 8.18 minutes (major enantiomer, minor enantiomer not observed), indicated that the reaction proceeded with >99% enantioselectivity.

Aufarbeitung

  1. additionTo this vigorously stirred suspension was added antracen-9-yl-methyl quininium chloride (0.071 g, 0.129 mmol)
  2. extractionthe reaction mixture was extracted with dichloromethane (3×)
  3. customThe crude product was purified by flash chromatography (0% to 5% ethyl acetate in cyclohexane)

Quellen und Nachweise

ORD-Eintrag
ord-e91fafd309fc4d83abc9a66e24a94a02
Quelldatensatz
uspto-grants-2016_01
Patentnummer
US09233920B2

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