Reaction #90428

Reaction equation

NH4Cl

Ethyl 8-methyl-3,4-dihydro-1H-pyrido[4,3-b]indole-2(5H)-carboxylate

Epibromohydrin

epibromohydrin

→

desired product

Yield 49.2%

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

Yield 49.2%

Conditions

Workup

1. 1
   Otherin anhydrous degassed THF
2. 2
   workup.ADDITIONA solution of n-BuLi (0.082 mL, 1.78 M in hexanes) was added dropwise
3. 3
   Temperatureto warm slowly to ambient temperature
4. 4
   workup.WAITAfter 3.5 h
5. 5
   workup.STIRRINGthe reaction was stirred overnight at ambient temperature
6. 6
   Otherto quench
7. 7
   Otherthe reaction
8. 8
   Extractionthe mixture was extracted with EtOAc (3×)
9. 9
   WashThe combined organic layers were washed with brine
10. 10
    Dryingdried over Na2SO4
11. 11
    Filtrationfiltered
12. 12
    Concentrationconcentrated
13. 13
    OtherThe crude residue was purified by chromatography (SiO2, 0-50% EtOAc/Hexane)

Procedure

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%).

Source