(R)-2-methyl-N-(oxetan-3-ylidene)propane-2-sulfinamide

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 3-bromo-5-iodopyridine (0.14 g, 0.493 mmol) in THF (2 mL) cooled at −78° C. was added nBuLi (462 μl, 0.74 mmol) dropwise over 5 min. The reaction mixture was stirred at −78° C. for 15 min, then (R)-2-methyl-N-(oxetan-3-ylidene)-propane-2-sulfinamide (0.1 g, 0.567 mmol) in THF (1 mL) was added dropwise. The reaction mixture was stirred at −78° C. for 10 min then allowed to warm up to RT. The mixture was quenched with water (2 mL) and extracted with EtOAc (2×10 mL). Combined organics were dried over Na2SO4, filtered and evaporated to dryness. The residue was purified by silica gel flash chromatography eluting with a 0 to 100% EtOAc-heptane gradient to give the title compound (0.096 g, 58%) as a light yellow oil. MS: 333.0 and 335.1 (M+H+). The reaction mixture was stirred at −78° C. for 10 min to warm up to RT The mixture was quenched with water (2 mL) extracted with EtOAc (2×10 mL) Combined organics were dried over Na2SO4 filtered evaporated to dryness The residue was purified by silica gel flash chromatography eluting with a 0 to 100% EtOAc-heptane gradient

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of Ti(OEt)4 (2.02 g, 7.53 mmol) in THF (20 mL) was added (R)-2-methylpropane-2-sulfinamide (0.854 g, 7.05 mmol) followed by oxetan-3-one (0.493 g, 6.84 mmol) in THF (5 mL) and the reaction mixture was heated to 50° C. over night. After cooling, the reaction mixture was diluted with EtOAc (50 mL) and a saturated solution of brine (20 mL) was slowly added under stirring. After 15 min, the mixture was filtered through a plug of Dicalite and washed with EtOAc. The organic phase was separated, dried over Na2SO4 and evaporated to dryness. The residue was purified by silica gel flash chromatography eluting with a 0 to 40% EtOAc-heptane gradient to give the title compound (0.242 g, 20%) as a light yellow oil. MS: 176.2 (M+H+). After cooling the mixture was filtered through a plug of Dicalite washed with EtOAc The organic phase was separated dried over Na2SO4 evaporated to dryness The residue was purified by silica gel flash chromatography eluting with a 0 to 40% EtOAc-heptane gradient