p-Toluenesulfonic acid → N-(1-(2-(Benzyloxy)-3-tert-butylphenyl)ethyl)2-methoxyaniline

Participants

Reaction Steps

A mixture of 21 (1.88 g, 7 mmol, 1.0 equiv), o-anisidine (0.86 g, 0.79 mL, 7 mmol, 1.0 equiv), toluene (35 mL) and a crystal of p-toluenesulfonic acid was refluxed for 4 hr with H2O removal (Dean-Stark trap). The mixture was cooled to room temperature and concentrated under reduced pressure to give crude imine 22 as a yellow-brown oil. Crude 22 was dissolved in THF (25 mL) and the solution cooled to ˜2° C. 3M MeMgBr in THF (5 mL, 15 mmol, 2.15 equiv) was added dropwise via syringe. A green color developed followed by a yellow-brown color. The reaction mixture was allowed to warm to room temperature and stirred overnight. The mixture was cooled to ˜10° C., quenched by the slow, dropwise addition of saturated NH4Cl solution (10 mL) then partitioned between EtOAc (100 mL) and H2O (20 mL). The organic phase was washed with brine (2×40 mL), dried over Na2SO4, filtered and the solution concentrated under reduced pressure to give a brown oil. The crude product was absorbed onto silica gel using dichloromethane and dry-loaded onto a column of silica gel (30 g) packed in heptanes. The column was eluted with heptanes (100 mL), 2% EtOAc/heptanes (200 mL) and 3% EtOAc/heptanes (200 mL). Product fractions were concentrated under reduced pressure to give 2.3 g (85%) 23 as a yellow oil.

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