Potassium Carbonate → (2R,3S)-2-(3-Chloro-4-cyano-2-propylphenylamino)-3-hydroxybutanoic acid

Temperature

80 °C

2-Chloro-4-fluoro-3-propylbenzonitrile (CAS 924626-89-1, 3.22 g, 16.3 mmol) was mixed together with H-D-Thr-OH (2.33 g, 19.6 mmol) in DMSO (30 mL) at room temperature. K2CO3 (4.73 g, 34.2 mmol) was added and the reaction mixture was stirred at 80° C. for 40 h. The reaction mixture was then cooled to room temperature and partitioned between water and EtOAc. The layers were separated and the aqueous extract was washed once with EtOAc. The aqueous extract was then acidified by slow addition of citric acid and stirred for 10 min at room temperature. The solution was extracted with EtOAc several times and the organic extracts were combined, washed with water, dried over Na2SO4, filtered, and concentrated in vacuo to obtain the crude product (0.650 g, 13% yield), which was carried on to the next step without further purification.

1. temperatureThe reaction mixture was then cooled to room temperature
2. custompartitioned between water and EtOAc
3. customThe layers were separated
4. extractionthe aqueous extract
5. washwas washed once with EtOAc
6. extractionThe aqueous extract
7. additionwas then acidified by slow addition of citric acid
8. stirringstirred for 10 min at room temperature
9. extractionThe solution was extracted with EtOAc several times
10. washwashed with water
11. dry with materialdried over Na2SO4
12. filtrationfiltered
13. concentrationconcentrated in vacuo

ORD record

ord-4af266d120964e22a6f9080975d44983

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08642632B2