Methyl iodide → 2-(Tert-butoxycarbonyl)-1-methyl-1,2,3,4-tetrahydroisoquinoline-8-carboxylic acid

Temperature

-78 °C

To a solution of 2-(tert-butoxycarbonyl)-1,2,3,4-tetrahydroisoquinoline-8-carboxylic acid (2.25 g) and tetramethylethylenediamine (1.347 mL) in tetrahydrofuran (40 mL) was added dropwise t-butyllithium (1.6M, 15.21 mL) at −78° C. The mixture was stirred at −78° C. for 40 minutes. To the resulting mixture was added iodomethane (5.07 mL) dropwise and the mixture was stirred at −78° C. for 3 hours, followed by stirring at room temperature overnight. The reaction mixture was quenched with saturated ammonium chloride. The reaction mixture was extracted with ethyl acetate (150 mL), and the organic layer was washed with brine (40 mL×3), dried over Na2SO4, filtered, and concentrated. The crude product was purified by flask chromotography (silica gel, 10% methanol/dichloromethane).

1. stirringthe mixture was stirred at −78° C. for 3 hours
2. stirringby stirring at room temperature overnight
3. customThe reaction mixture was quenched with saturated ammonium chloride
4. extractionThe reaction mixture was extracted with ethyl acetate (150 mL)
5. washthe organic layer was washed with brine (40 mL×3)
6. dry with materialdried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated
9. customThe crude product was purified by flask chromotography (silica gel, 10% methanol/dichloromethane)

ORD record

ord-0748f7e066884eea9c191a6b692f6cf5

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09266877B2