反应详情

温度

0 °C

To a cooled solution of 2,4,4-trimethyl-1,2,3,4-tetrahydro-isoquinolin-7-ylamine (prepared essentially as described in PCT International Application Publication Numbers WO 00/009,486, WO 00/007,993 or WO 98/41507; 330 mg, 1.734 mmol) in 75% aqueous H2SO4, add NaNO2 (132 mg, 1.91 mmol) in 1 ml of water, dropwise. Stir the solution at 0° C. for 30 minutes. Add CuBr (298 mg, 2.08 mmol) and 48% HBr (2 ml). Stir the mixture at 0° C. for 15 minutes. Heat the mixture at 60° C. for 30 minutes. Cool to room temperature, adjust the pH to 9-10, and extract with EtOAc. Wash with brine, dry the solution (Na2SO4), and concentrate under reduced pressure. Purify the residue by flash column chromatography eluting with EtOAc:Hexanes-(1:1) to afford 7-bromo-2,4,4-trimethyl-1,2,3,4-tetrahydro-isoquinoline.

1. stirringStir the mixture at 0° C. for 15 minutes
2. temperatureHeat the mixture at 60° C. for 30 minutes
3. temperatureCool to room temperature
4. extractionextract with EtOAc
5. washWash with brine
6. dry with materialdry the solution (Na2SO4)
7. concentrationconcentrate under reduced pressure
8. customPurify the residue by flash column chromatography
9. washeluting with EtOAc:Hexanes-(1:1)