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-f5bd7ac5fde146f290295e742eda1508

Source dataset

uspto-grants-2015_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08940737B2