Reaktion #325759

Reaktionsgleichung

Cs2CO3

2-chloro-4-fluoro-3-methylbenzonitrile

(2R,3S)-2-amino-3-(benzyloxy)-4,4,4-trifluorobutanoic acid hydrochloride salt

→

(2R,3S)-3-(benzyloxy)-2-(3-chloro-4-cyano-2-methylphenylamino)-4,4,4-trifluorobutanoic acid

Ausbeute 21.9%

Lösungsmittel

DMSO

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturAfter cooling to room temperature
2. 2
   Extraktionextracted with 10% EtOAc in hexanes (2×50 mL)
3. 3
   Extraktionextracted with EtOAc (2×100 mL)
4. 4
   WaschenThe EtOAc extracts were washed with water, brine
5. 5
   Trocknendried over Na2SO4
6. 6
   SonstigeRemoval of the solvent
7. 7
   Sonstigegave a residue, which
8. 8
   Sonstigewas purified by flash chromatography

Vorschrift

Cs2CO3 (3.5 g, 10.7 mmol) was added to a mixture of 2-chloro-4-fluoro-3-methylbenzonitrile (0.79 g, 4.65 mmol) and (2R,3S)-2-amino-3-(benzyloxy)-4,4,4-trifluorobutanoic acid hydrochloride salt (0.93 g, 3.1 mmol) in DMSO (18 mL) at room temperature. The resulting mixture was heated to 80° C. and stirred for 2 days. After cooling to room temperature, the reaction mixture was poured into ice-water (150 mL) and extracted with 10% EtOAc in hexanes (2×50 mL). The aqueous phase was acidified to pH=2˜3 with 2N HCl and extracted with EtOAc (2×100 mL). The EtOAc extracts were washed with water, brine and dried over Na2SO4. Removal of the solvent gave a residue, which was purified by flash chromatography to afford the crude (2R,3S)-3-(benzyloxy)-2-(3-chloro-4-cyano-2-methylphenylamino)-4,4,4-trifluorobutanoic acid (280 mg) as a mixture.

Quelle