Toluene → Tert-butyl 4-(4-formylphenyl)piperazine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a −78° C. solution of 1-(4-bromophenyl)-4-(tert-butoxycarbonyl)piperazine (9.98 g, 29.2 mmol, prepared as described in Example 1) in TI (70 mL) and toluene (70 mL) was added nBuLi (1.6 M in hexanes, 19 mL, 30.4 mmol) at a rate to maintain an internal temperature below −65° C. The resulting solution was stirred 15 min, then treated with DMF (5 mL). The mixture was stirred 30 min at −78° C., then allowed to warm to 0° C., quenched with saturated ammonium chloride and extracted with ethyl acetate. The organic phase was washed with brine, dried over MgSO4 and concentrated. The crude material was crystalized from dichloromethane/ether/hexanes to give 4-[4-(tert-butoxycarbonyl)-1-piperazinyl]benzaldehyde. The filtrates were purified by flash chromatography (30% ethyl acetate/hexanes to 60% ethyl acetate/hexanes) to provide an additional 2.16 g of the desired product.

Provenance & Evidence