2-Methoxyaniline → HCID 67105335, compound

Participants

Reaction Steps

A mixture of 24 (3.0 g, 10 mmol, 1.0 equiv), o-anisidine (1.3 g, 1.2 mL, 100 mmol, 1.0 equiv), toluene (45 mL) containing a crystal of p-toluenesulfonic was refluxed for 5.5 hr with H2O removal (Dean-Stark trap). The mixture was cooled to room temperature and stirred overnight. The mixture was concentrated under reduced pressure to give crude imine 25 as a yellow-brown oil. Crude 25 was dissolved in THF (75 mL) and the solution cooled to −2° C. 1.8M phenyllithium in di-n-butylether (15 mL, 27 mmol, 2.7 equiv) was added dropwise via syringe at −2° C. to 0° C. The yellow-brown solution was allowed to warm to room temperature and stirred 1.5 hr. The mixture was cooled to ˜10° C., quenched by the slow, dropwise addition of saturated NH4Cl solution (20 mL) then partitioned between 1:1 EtOAc heptanes (150 mL) and H2O (25 mL). The organic phase was washed with brine (50 mL), dried over Na2SO4, filtered and the solution concentrated under reduced pressure to give a yellow oil. The crude product was absorbed onto silica gel using dichloromethane and dry-loaded onto a column of silica gel (100 g) packed in hexanes. The column was eluted with hexanes (500 mL), 1% MTME/hexanes (1000 mL) and 2% MTBE/hexanes (1500 mL). Product fractions were concentrated under reduced pressure to give a yellowish-white solid that was pumped under high vacuum overnight to give 3.6 g (75%) of 26.

Provenance & Evidence