Tetrabenazine → HCID 15686747、化合物

温度

20 °C

Trimethylsilylacetylene (2 eqs.; 20.4 mmol; 2.88 mL) was dissolved in 80 mL of dry THF and stirred under a nitrogen atmosphere at -5° to 0° C. n-Butyl lithium (20.4 mmol, 12.72 mL) was added dropwise with stirring followed by dropwise addition of a solution of 3-isobutyl-9-,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-benzo[a]quinolizin-2-one (TBZ) in 30 mL dry THF. The reaction mixture was stirred at -5° to 0° C. for 1 h, allowed to warm slowly to 20° C., and stirred for 2 h at 20° C. The reaction was quenched while cold with saturated NH4Cl. The solvent was evaporated under reduced pressure and the resulting aqueous solution was extracted with ethyl acetate (3×100 mL). The organic phase was washed with water (2×50 mL) and brine (50 mL) and concentrated. The residue was dissolved in 30 mL MeOH and 5 mL 5N KOH, and heated to 65° C. with stirring for 30 min. The reaction was cooled and quenched with NH4Cl. The methanol was evaporated and the aqueous phase extracted with ethyl acetate (3×75 mL). The organic phase was washed with water (50 mL) and brine (50 mL), dried over Na2SO4, and concentrated to yield the product (53.7%) as slightly brown solid.

1. additionwas added dropwise
2. stirringThe reaction mixture was stirred at -5° to 0° C. for 1 h
3. stirringstirred for 2 h at 20° C
4. customThe reaction was quenched while cold with saturated NH4Cl
5. customThe solvent was evaporated under reduced pressure
6. extractionthe resulting aqueous solution was extracted with ethyl acetate (3×100 mL)
7. washThe organic phase was washed with water (2×50 mL) and brine (50 mL)
8. concentrationconcentrated
9. dissolutionThe residue was dissolved in 30 mL MeOH
10. temperature5 mL 5N KOH, and heated to 65° C.
11. stirringwith stirring for 30 min
12. temperatureThe reaction was cooled
13. customquenched with NH4Cl
14. customThe methanol was evaporated
15. extractionthe aqueous phase extracted with ethyl acetate (3×75 mL)
16. washThe organic phase was washed with water (50 mL) and brine (50 mL)
17. dry with materialdried over Na2SO4
18. concentrationconcentrated

ORDレコード

ord-9093b1b88b7744acb7abdb3a45f48bfd

出典データセット

uspto-grants-1994_01

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US05278308