(NE,R)-2-methyl-N-[(4-pyrimidin-5-yloxyphenyl)methylidene]propane-2-sulfinamide → 2-methyl-N-((S)-1-(4-(pyrimidin-5-yloxy)phenyl)ethyl)propane-2-sulfinamide

Temperature

-20 °C

A solution of (R,E)-2-methyl-N-(4-(pyrimidin-5-yloxy)benzylidene)propane-2-sulfinamide (830 mg, 2.74 mmol) in DCM (6.72 mL) was cooled to −40° C. To the solution was added methylmagnesium bromide (3M in diethylether; 1.81 mL) dropwise over 10 min. Additional DCM (5 mL) were added to retain stirring. The yellow suspension was stirred at −40° C. for ˜30 min while warming to −20° C. The mixture was cooled to −40° C. and additional methylmagnesium bromide (3M in diethylether; 1.8 mL) was added. The suspension was stirred for ˜3 hour while slowly warming to −20° C. The mixture was cooled to ˜−40° C., and additional methylmagnesium bromide (3M in diethylether; 0.4 mL) was added. The suspension was stirred for 30 min and allowed to warm to −10° C. The mixture was quenched slowly over 10 min with saturated aqueous NH4Cl solution (10 mL). The mixture was diluted with saturated aqueous NH4Cl solution (30 mL) and water (15 mL). The separated aqueous phase was extract with DCM (2×75 mL). The combined organic layers were washed with brine (50 mL), dried over Na2SO4, filtered off and concentrated under reduced pressure. The residue was purified by column chouromatography [SiO2, 40 g, heptane/ethyl acetate followed by 5% MeOH in EtOAc] providing 2-methyl-N—((S)-1-(4-(pyrimidin-5-yloxy)phenyl)ethyl)propane-2-sulfinamide (55 mg; purity ˜87%) as an off-white solid. LCMS m/z 320.0 (M+H)+, Rt 0.69 min.

1. stirringThe yellow suspension was stirred at −40° C. for ˜30 min
2. temperatureThe mixture was cooled to −40° C.
3. stirringThe suspension was stirred for ˜3 hour
4. temperaturewhile slowly warming to −20° C
5. temperatureThe mixture was cooled to ˜−40° C.
6. stirringThe suspension was stirred for 30 min
7. temperatureto warm to −10° C
8. customThe mixture was quenched slowly over 10 min with saturated aqueous NH4Cl solution (10 mL)
9. additionThe mixture was diluted with saturated aqueous NH4Cl solution (30 mL) and water (15 mL)
10. extractionThe separated aqueous phase was extract with DCM (2×75 mL)
11. washThe combined organic layers were washed with brine (50 mL)
12. dry with materialdried over Na2SO4
13. filtrationfiltered off
14. concentrationconcentrated under reduced pressure
15. customThe residue was purified by column chouromatography [SiO2, 40 g, heptane/ethyl acetate followed by 5% MeOH in EtOAc]

ORD record

ord-211fcd20b3cd4efc842ba38bf9f454c2

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08957068B2