Citric Acid → (2r,3s)-2-(4-Cyano-2-methyl-3-(trifluoromethyl)phenylamino)-3-hydroxybutanoic acid
Reaktionsgleichung
F[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([C:10]([F:13])([F:12])[F:11])[C:3]=1[CH3:14].C1[C:20]([CH2:21][C@@H:22]([NH2:26])[C:23]([OH:25])=[O:24])=CC=C(OC2C=CC(O)=CC=2)C=1.C([O-])([O-])=[O:36].[K+].[K+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CS(C)=O>[C:6]([C:5]1[CH:8]=[CH:9][C:2]([NH:26][C@H:22]([C@@H:21]([OH:36])[CH3:20])[C:23]([OH:25])=[O:24])=[C:3]([CH3:14])[C:4]=1[C:10]([F:13])([F:12])[F:11])#[N:7]Komponenten
Edukt 4
Produkt 1
Reagenzien, Katalysatoren, Lösungsmittel 1
Reaktionsbedingungen
- Temperatur
- 75 °C
Versuchsvorschrift
4-fluoro-3-methyl-2-(trifluoromethyl)benzonitrile (1.0 g, 4.92 mmol) and D-theronine (703 mg, 90 mmol) were added to DMSO (15 mL). K2CO3 (3.26 g) was added to the reaction mixture and stirred at 75° C. for 24 h. The reaction mixture was cooled to room temperature and poured slowly in to a 10% citric acid solution and stirred for 10 min at room temperature. The solution was extracted with EtOAc several times to give the crude product. The crude product was chromatographed with a gradient of hexanes/EtOAc and then with EtOAc, 100% to give the final product (400 mg). 1H NMR (500 MHz, acetone-d6, δ in ppm) 7.62 (d, J=9 Hz, 1H), 6.98 (d, J=9 Hz, 1H), 5.52 (d, J=9 Hz, 1H), 4.52 (m, 1H), 4.32 (m, 1H), 2.35 (s, 3H), 1.35 (d, J=6 Hz, 3H).
Aufarbeitung
- temperatureThe reaction mixture was cooled to room temperature
- stirringstirred for 10 min at room temperature
- extractionThe solution was extracted with EtOAc several times
- customto give the crude product
- customThe crude product was chromatographed with a gradient of hexanes/EtOAc
Quellen und Nachweise
- ORD-Eintrag
- ord-eda7f568cf45452aa739ab28d2460750
- Quelldatensatz
- uspto-grants-2014_01
- Patentnummer
- US08629167B2
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