Ethyl Acetate → Ethyl 2-[(2'-cyano-2-methoxybiphenyl-4-yl)methyl]-3-oxohexanoate

To a solution of ethyl 2′-cyano-2-methoxybiphenyl-4-carboxylate (0.28 g) in tetrahydrofuran (10 mL) was added lithium borohydride (0.22 g), and the mixture was stirred at room temperature for 15 hr. To the reaction mixture were added ethyl acetate and saturated aqueous ammonium chloride solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated. The residue was dissolved in toluene (5 mL), phosphorus tribromide (0.050 mL) was added, and the mixture was stirred for 1 hr. Ethyl acetate and water were added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated. This was dissolved in tetrahydrofuran (2 mL), the mixture was added dropwise to a solution of ethyl 3-oxohexanoate (0.25 g) and 60% sodium hydride (0.047 g) in tetrahydrofuran (2 mL) at 0° C., and the mixture was stirred at room temperature for 15 hr. To the reaction mixture were added ethyl acetate and saturated aqueous ammonium chloride solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated. The residue was purified by silica gel column chromatography to give the title compound as a pale-yellow amorphous solid (0.26 g, 85%).

1. extractionthe mixture was extracted with ethyl acetate
2. washThe organic layer was washed with water and saturated brine
3. dry with materialdried over anhydrous magnesium sulfate
4. concentrationconcentrated
5. dissolutionThe residue was dissolved in toluene (5 mL)
6. additionphosphorus tribromide (0.050 mL) was added
7. stirringthe mixture was stirred for 1 hr
8. additionEthyl acetate and water were added to the reaction mixture
9. extractionthe mixture was extracted with ethyl acetate
10. washThe organic layer was washed with water and saturated brine
11. dry with materialdried over anhydrous magnesium sulfate
12. concentrationconcentrated
13. dissolutionThis was dissolved in tetrahydrofuran (2 mL)
14. additionthe mixture was added dropwise to a solution of ethyl 3-oxohexanoate (0.25 g) and 60% sodium hydride (0.047 g) in tetrahydrofuran (2 mL) at 0° C.
15. stirringthe mixture was stirred at room temperature for 15 hr
16. additionTo the reaction mixture were added ethyl acetate and saturated aqueous ammonium chloride solution
17. extractionthe mixture was extracted with ethyl acetate
18. washThe organic layer was washed with water and saturated brine
19. dry with materialdried over anhydrous magnesium sulfate
20. concentrationconcentrated
21. customThe residue was purified by silica gel column chromatography

ORD record

ord-eba9d83020e3492a853f82fc0671e9fe

Source dataset

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09115136B2