Epibromohydrin → ethyl 8-Methyl-5-(oxiran-2-ylmethyl)-3,4-dihydro-1H-pyrido[4,3-b]indole-2(5H)-carboxylate

Temperature

-78 °C

Ethyl 8-methyl-3,4-dihydro-1H-pyrido[4,3-b]indole-2(5H)-carboxylate (0.025 g, 0.097 mmol) was dissolved in anhydrous degassed THF and was cooled to −78° C. A solution of n-BuLi (0.082 mL, 1.78 M in hexanes) was added dropwise and the reaction was stirred at −78° C. for 30 min. Epibromohydrin (0.016 mL, 0.194 mmol) was added and the reaction was allowed to warm slowly to ambient temperature. After 3.5 h, epibromohydrin (0.008 mL, 0.097 mmol) was added and the reaction was stirred overnight at ambient temperature. Upon completion, saturated aqueous NH4Cl was added to quench the reaction and the mixture was extracted with EtOAc (3×). The combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated. The crude residue was purified by chromatography (SiO2, 0-50% EtOAc/Hexane) to afford the desired product (15 mg, 49%).

1. customin anhydrous degassed THF
2. additionA solution of n-BuLi (0.082 mL, 1.78 M in hexanes) was added dropwise
3. temperatureto warm slowly to ambient temperature
4. waitAfter 3.5 h
5. stirringthe reaction was stirred overnight at ambient temperature
6. customto quench
7. customthe reaction
8. extractionthe mixture was extracted with EtOAc (3×)
9. washThe combined organic layers were washed with brine
10. dry with materialdried over Na2SO4
11. filtrationfiltered
12. concentrationconcentrated
13. customThe crude residue was purified by chromatography (SiO2, 0-50% EtOAc/Hexane)

ORD record

ord-f7e3642a018b444cb6687f914c087120

Source dataset

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08748473B2