N-Methyl-o-phenylenediamine → HCID 86732072, compound

Participants

Reaction Steps

To a solution of N1-methylbenzene-1,2-diamine (5.08 g, 41.5 mmol) in toluene (100 mL) was added a 2M solution of trimethylaluminum (22.85 ml, 45.7 mmol) in toluene dropwise over 2 h with periodic cooling in an ice bath to prevent an exotherm. After addition was complete, the resulting dark brown mixture was warmed to room temperature and stirred for 15 min. The mixture was re-cooled in an ice bath and a solution of 6-3 (5 g, 20.8 mmol) in toluene (20 mL) was added drop-wise over 2 h, after which the reaction was warmed to room temperature. After stirring for 18 h, the reaction was cooled in an ice bath and slowly quenched with water. The mixture was filtered through a pad of celite washing with ethyl acetate. The filtrate was repeatedly washed with saturated copper (II) sulfate solution until a yellow orange organic layer was obtained and no N1-methylbenzene-1,2-diamine was observed by LCMS. The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo to give the crude product which was purified by silica gel chromatography (0-100% EtOAc/hexanes) to afford racemic 6-4. The racemic compound was further purified by preparative chiral SFC on a ChiralCel OJ-H column (3 cm id×25 cm length) eluting with 70% carbon dioxide/30% methanol with 0.1% triethylamine modifier in isocratic mode at 80 mL/min. The first eluting peak was identified as the desired R,R enantiomer (6-4) and was used in subsequent steps. 1H NMR (400 MHz, CDCl3) δ 7.71-7.66 (m, 1H), 7.31-7.23 (m, 3H), 7.19 (s, 1H), 3.83 (s, 3H), 2.86-2.79 (m, 2H), 2.67 (s, 3H), 1.96 (m, 2H); MS: m/z=299.2 (M+H).

Provenance & Evidence