Methyl iodide → N-(5-tert-butyl-isoxazol-3-yl)-2-methyl-2-(4-methyl-tetrahydro-pyran-4-sulfonyl)-propionamide

Temperature

-78 °C

To a solution of 202 mg (0.56 mmol) of N-(5-tert-butyl-isoxazol-3-yl)-2-methyl-2-(tetrahydro-pyran-4-sulfonyl)-propionamide (prepared according to Method E) in anhydrous THF (10 mL) at −78° C. under nitrogen atmosphere were added 0.8 mL (1.4 mmol) of lithium diisopropylamide (1.8 M solution in THF/heptane/ethylbenzene) and the reaction was stirred at −78° C. for 0.5 h. Then 0.1 mL (1.6 mmol) of methyl iodide were added in one portion and stirring was continued for further 0.5 h at −78° C., before the reaction was warmed to room temperature. After 18 h at room temperature the reaction was quenched by the addition of saturated aqueous NH4Cl solution (25 mL). The mixture was extracted with ethyl acetate (3×25 mL). The organic extracts were combined, dried over Na2SO4 and filtered. The filtrate was concentrated under reduced pressure and the residue purified by mass-triggered preparative LCMS to afford 31 mg of N-(5-tert-butyl-isoxazol-3-yl)-2-methyl-2-(4-methyl-tetrahydro-pyran-4-sulfonyl)-propionamide.

1. stirringstirring
2. waitwas continued for further 0.5 h at −78° C., before the reaction
3. temperaturewas warmed to room temperature
4. customAfter 18 h at room temperature the reaction was quenched by the addition of saturated aqueous NH4Cl solution (25 mL)
5. extractionThe mixture was extracted with ethyl acetate (3×25 mL)
6. dry with materialdried over Na2SO4
7. filtrationfiltered
8. concentrationThe filtrate was concentrated under reduced pressure
9. customthe residue purified by mass-triggered preparative LCMS

ORD record

ord-d9c13e77491a43708fb87a0ba95d796f

Source dataset

uspto-grants-2011_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07928123B2