Citric Acid → (2r,3s)-2-(4-Cyano-2-methyl-3-(trifluoromethyl)phenylamino)-3-hydroxybutanoic acid

HRID 1254703

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

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-daca09fcf85c4db8b583f3b6b21b2510
Quelldatensatz: uspto-grants-2013_06
DOI: 10.6084/m9.figshare.5104873.v1
Patentnummer: US08455525B2

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