Ethyl Acetate → HCID 49865452, compound

Participants

Reaction Steps

To a solution of 2-chlorobenzyl)(4-nitrophenyl)sulfane (1.0 equivalent) in DCM at 0° C. was added m-CPBA (3.0 equivalents). After 30 min, the ice bath was removed. The reaction was followed by thin liquid chromatography (TLC). The reaction was added to DCM:NaHCO3 (sat'd) (1:1) and the organic layer was separated. After washing the organic layer with water (2×) and brine, it was dried (MgSO4), filtered and concentrated to provide 1-chloro-2-(((4-nitrophenyl)sulfonyl)methyl)benzene. Analytical: Rf=0.72 (50% EtOAc/hexanes); LCMS (Method 2): RT=1.41 min, >90% @ 254 nM, m/z=333.8 [M+Na]+. Step 3: To a solution of 1-chloro-2-(((4-nitrophenyl)sulfonyl)methyl)benzene in EtOAc (0.3 M) was added 5% Pd/C (˜0.1 equivalent). An H2 atmosphere (1 atm) was applied to the rxn mixture. After 12 h, TLC confirmed loss of starting material, so rxn was filtered through Celite and concentrated. The crude residue, 4-(((2-chlorobenzyl)sulfonyl)aniline, was carried through without further purification (85-95% yield over 2 steps). Analytical: Rf=0.40 (50% EtOAc/hexanes); LCMS (Method 2): RT=1.25 min, >98% @ 254 nM, m/z=281.9 [M+H]+. Step 4: To a solution of the 4-(((2-chlorobenzyl)sulfonyl)aniline in DMF:DIEA (4:1) (0.1 M). The appropriate acid chloride (1.0 equivalent) was added and after 12 h at 85° C., N-(4-(((2-chlorobenzyl)sulfonyl)phenyl)picolinamide was directly purified by mass-guided preparative HPLC.

Provenance & Evidence