2-(Tributylstannyl)pyrimidine → (S)-N-((S)-(3-fluoro-4-(trifluoromethyl)phenyl)-(pyrimidin-2-yl)methyl)-2-methylpropane-2-sulfinamide

Temperature

-78 °C

To a solution of 2-(tributylstannyl)pyrimidine (425 mg, 1.151 mmol) in THF (3 mL) at −78° C. was added n-butyllithium (0.720 mL, 1.151 mmol) (1.6 M in hexanes). The reaction was stirred at −78° C. for 1.5 h and then (S,E)-N-(3-fluoro-4-(trifluoromethyl)benzylidene)-2-methylpropane-2-sulfinamide (408 mg, 1.382 mmol) in THF (1 mL) was added. The cooling bath was then removed as the reaction was allowed to warm to rt and stirred for 1 h. LCMS showed 2 products with a ratio of 10:1. The reaction was quenched with saturated aqueous NH4Cl (5 mL) and H2O (5 mL). The reaction mixture was extracted with EtOAc (2×5 mL). The organic layers were combined, dried (MgSO4), and concentrated to give the product. Purification by ISCO (12 g SiO2, 20-80% EtOAc/hexanes) gave the major product, (S)—N—((S)-(3-fluoro-4-(trifluoromethyl)phenyl)-(pyrimidin-2-yl)methyl)-2-methylpropane-2-sulfinamide.

1. customThe cooling bath was then removed as the reaction
2. temperatureto warm to rt
3. stirringstirred for 1 h
4. customThe reaction was quenched with saturated aqueous NH4Cl (5 mL) and H2O (5 mL)
5. extractionThe reaction mixture was extracted with EtOAc (2×5 mL)
6. dry with materialdried (MgSO4)
7. concentrationconcentrated
8. customto give the product
9. customPurification by ISCO (12 g SiO2, 20-80% EtOAc/hexanes)

ORD record

ord-a5cf99c796a8437bb8ed3732b0d003c6

Source dataset

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09096527B2