Water → (2R,3R)-2-(3-chloro-4-cyano-2-methylphenylamino)-3-hydroxybutanoic acid

HRID 470836

Reaktionsgleichung

Reaktionsgleichung von HRID 470836
C([O-])([O-])=O.[K+].[K+].[Cl:7][C:8]1[C:15]([CH2:16]C)=[C:14](F)[CH:13]=[CH:12][C:9]=1[C:10]#[N:11].[NH2:19][C@@H:20]([C:24]([OH:26])=[O:25])[C@@H:21]([CH3:23])[OH:22].O>CS(C)=O>[Cl:7][C:8]1[C:15]([CH3:16])=[C:14]([NH:19][C@H:20]([C@H:21]([OH:22])[CH3:23])[C:24]([OH:26])=[O:25])[CH:13]=[CH:12][C:9]=1[C:10]#[N:11]

Komponenten

6

Edukt 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 90624D-AllothreonineHCID 579086952-Chloro-3-ethyl-4-fluorobenzonitrile

Produkt 1

HCID 57908625(2R,3R)-2-(3-chloro-4-cyano-2-methylphenylamino)-3-hydroxybutanoic acidAusbeute 47 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 679Dimethyl SulfoxideLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

K2CO3 (3.15 g, 22.8 mmol) was added to a solution of 2-chloro-3-ethyl-4-fluorobenzonitrile (2.1 g, 11.4 mmol) and D-allo-threonine (2.04 g, 17.1 mmol) in DMSO (25 mL) at room temperature The reaction mixture was heated to 80° C. and stirred for 72 h then allowed to cool to room temperature. H2O (200 mL) was added and the brown solution was extracted with MTBE (200 mL). The aqueous layer was cooled to 0° C. and solid citric acid monohydrate was added in 200 mg portions until the evolution of as ceased. The aqueous layer was then extracted with EtOAc (3×200 mL). The combined organic layers were washed with brine (2×300 mL), dried with Na2SO4, filtered and concentrated to provide the title compound (1.44 g, 32%); 1H NMR (500 MHz, acetone-d6, δ in ppm) 7.47 (d, J=8.6 Hz, 2H), 6.70 (d, J=8.6 Hz, 2H), 5.46 (d, J=8.7 Hz, 1H), 4.55-4.43 (m, 1H), 4.27 (dd, J=5.9 Hz, 8.7 Hz, 1H), 2.90-2.81 (m, 2H), 1.33 (d, J=6.3 Hz, 3H), 1.21 (t, J=7.6 Hz, 3H).

Aufarbeitung

  1. temperatureto cool to room temperature
  2. extractionthe brown solution was extracted with MTBE (200 mL)
  3. temperatureThe aqueous layer was cooled to 0° C.
  4. additionsolid citric acid monohydrate was added in 200 mg portions until the evolution of
  5. extractionThe aqueous layer was then extracted with EtOAc (3×200 mL)
  6. washThe combined organic layers were washed with brine (2×300 mL)
  7. dry with materialdried with Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-680d942c30a54ccd9e2154a025a0722e
Quelldatensatz
uspto-grants-2014_01
Patentnummer
US08629167B2

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