Hydrochloric Acid → HCID 22261879, compound

To a solution of ethyl (1-naphthoyl)acetate (10.2 g, 39.9 mmol) in acetonitrile (100 ml) was added 4-(trifluoromethyl)benzyl bromide (9.54 g, 39.9 mmol) and the mixture was stirred overnight at room temperature. The reaction solution was concentrated, diluted with water (500 ml) and extracted with ethyl acetate (300 ml×2). The extract was washed with saturated brine, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:toluene=1:1). To a solution of the crude product of the obtained monoalkyl form (7.46 g, 18.63 mmol) in ether (100 ml) was added a solution of Zn(NH4)2 in ether (100 ml), which was prepared from zinc chloride (5.07 g, 37.3 mmol) and sodium borohydride (2.82 g, 74.5 mmol), and the mixture was stirred at room temperature for 30 min. The reaction solution was ! poured into 1N aqueous hydrochloric acid solution (100 ml) and extracted with ethyl acetate (300 ml×2). The extract was washed with saturated brine, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (toluene). To a solution of the crude product of the obtained reduced compound (3.74 g, 9.29 mmol) in methanol (40 ml) was added 1N aqueous sodium hydroxide solution (20 ml, 20 mmol) and the mixture was stirred at room temperature for 4 hrs. The reaction solution was poured into 1N aqueous hydrochloric acid solution (40 ml) and extracted with ethyl acetate (100 ml×2). The extract was washed with saturated brine, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The residue was recrystallized from diisopropyl ether-hexane to give (2RS,3RS)-3-hydroxy-3-(1-naphthalenyl)-2-((4-(trifluoromethyl)phenyl)methyl)propionic acid (2.48 g, 16%).

1. concentrationThe reaction solution was concentrated
2. additiondiluted with water (500 ml)
3. extractionextracted with ethyl acetate (300 ml×2)
4. washThe extract was washed with saturated brine
5. dry with materialdried over anhydrous magnesium sulfate
6. customevaporated under reduced pressure
7. customThe residue was purified by silica gel column chromatography (hexane:toluene=1:1)
8. additionTo a solution of the crude product of the obtained monoalkyl form (7.46 g, 18.63 mmol) in ether (100 ml) was added a solution of Zn(NH4)2 in ether (100 ml), which
9. stirringthe mixture was stirred at room temperature for 30 min
10. extractionextracted with ethyl acetate (300 ml×2)
11. washThe extract was washed with saturated brine
12. dry with materialdried over anhydrous magnesium sulfate
13. customevaporated under reduced pressure
14. customThe residue was purified by silica gel column chromatography (toluene)
15. stirringthe mixture was stirred at room temperature for 4 hrs
16. extractionextracted with ethyl acetate (100 ml×2)
17. washThe extract was washed with saturated brine
18. dry with materialdried over anhydrous magnesium sulfate
19. customevaporated under reduced pressure
20. customThe residue was recrystallized from diisopropyl ether-hexane

ORD record

ord-c43b43a286c64d959ba13d8cc80a69be

Source dataset

uspto-grants-2006_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06982348B2