Ammonium Chloride → HCID 90372751, compound

Participants

Reaction Steps

To a cooled (−78° C.) solution of (E)-1,1-dimethyl-2-(1,1,1-trifluoropropan-2-ylidene)hydrazine (12.78 g, 83 mmol) in THF (80 mL) was added N-1,N-1,N-2,N2-tetramethylethane-1,2-diamine (9.64 g, 83 mmol) followed by lithium diisopropylamide, 2.0M solution in heptane/tetrahydrofuran/ethylbenzene (41.5 mL, 83 mmol) via syringe, and stirred for 60 min. In a second flask, a solution of (R,E)-N-(1-(2,3-difluorophenyl)-2-fluoroethylidene)-2-methylpropane-2-sulfinamide (11.5 g, 41.5 mmol) in toluene (50 mL) was treated with trimethylaluminum solution, 2.0M in toluene (20.74 mL, 41.5 mmol) at −78° C. After stirred for 10 min, this solution was cannulated to the solution containing hydrazone at −78° C. The reaction mixture was stirred at this temperature for 3 h. Saturated NH4Cl solution was added to quench the reaction. The resulted suspension was allowed to warm to room temperature and then filtered through a pad of celite. The filtrate was extracted with EtOAc (3×). The organic extracts were combined, washed with brine, dried over sodium sulfate and filtered. The filtrate was concentrated and purified by silica gel column (0-50% EtOAc/hexane) to afford (R)-N-((Z)-2-(2,3-difluorophenyl)-4-(2,2-dimethylhydrazono)-1,5,5,5-tetrafluoropentan-2-yl)-2-methylpropane-2-sulfinamide (9.0 g, 20.5 mmol) as yellow oil. The ratio of the two diastereoisomers was about 9:1 based on LCMS. MS m/z=432.2 [M+H]+. Calculated for C17H23F6N3OS: 431.4

Provenance & Evidence