Hydrochloric Acid → 5-Chloro-N-((2R)-2-hydroxy-3-((4-(3-oxo-4-morpholinyl)phenyl)amino)propyl)-2-thiophenecarboxamide

Temperature

0 °C

Under an atmosphere of nitrogen to a suspension of 1.65 g of 5-chloro-thiophene-2-carboxylic acid (MW=162.60; 1.2 eq.) in 50 mL of methylenechloride were added 1.62 g N,N′-carbonyldiimidazole (MW=162.15; 1.2 eq.) and the reaction mixture was stirred for 2 h. To the resulting solution of the azolide were added 2.41 g of 4-[4-((R)-3-amino-2-hydroxy-propylamino)-phenyl]-morpholin-3-one hydrochloride (MW=301.78; 1 eq.) and stirring at ambient temperature was continued for 4 h. Then 50 mL of 1 M aqueous hydrochloride were added. After 5 min of stirring, the layers were separated. The organic layer was extracted once more with 25 mL of 1 M hydrochloric acid. The combined aqueous layers were washed with 25 mL of methylenechloride and neutralized by the addition of approx. 15 mL of 5 M sodium hydroxide. The resulting suspension was stirred for 1 h at ambient temperature, then cooled to 0° C. After stirring in an ice bath for 2 h, the precipitate was isolated by filtration, washed with 10 mL of water and the wet product was dried in vacuo at 40° C.

1. stirringstirring at ambient temperature
2. waitwas continued for 4 h
3. stirringAfter 5 min of stirring
4. customthe layers were separated
5. extractionThe organic layer was extracted once more with 25 mL of 1 M hydrochloric acid
6. washThe combined aqueous layers were washed with 25 mL of methylenechloride
7. additionneutralized by the addition of approx. 15 mL of 5 M sodium hydroxide
8. stirringThe resulting suspension was stirred for 1 h at ambient temperature
9. stirringAfter stirring in an ice bath for 2 h
10. customthe precipitate was isolated by filtration
11. washwashed with 10 mL of water
12. customthe wet product was dried in vacuo at 40° C.

ORD record

ord-6cfdf278bd9d457f8bd7ddb34439c41f

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09221771B2