Reacción #41828

Ecuación de reacción

NaOH

4-formyl-benzoyl chloride

NaOH

isopropyl piperazine dihydrochloride salt

→

4-(4-isopropyl-piperazine-1-carbonyl)-benzaldehyde

Rendimiento 101.0%

Disolventes

toluene

H2O

toluene

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturato warm to room temperature over 16 h
2. 2
   Temperaturacooled to 0° C.
3. 3
   OtroThe phases were separated
4. 4
   Extracciónthe aqueous layer was extracted with toluene (2×200 mL)
5. 5
   Lavadowashed with brine (200 mL)
6. 6
   Concentraciónconcentrated

Procedimiento

A solution of NaOH (24.0 g, 0.600 mol) in de-ionized H2O (240 mL) and toluene (60 mL) at 0° C. was treated with isopropyl piperazine dihydrochloride salt (39.0 g, 194 mmol). The resulting biphasic solution was stirred at 0° C. for 30 min. A solution of 4-formyl-benzoyl chloride in toluene was added in a slow stream via an addition funnel over 1 h, with vigorous mechanical agitation. The mixture was allowed to warm to room temperature over 16 h, then cooled to 0° C., and the pH adjusted to 10 with 1 N NaOH. The phases were separated and the aqueous layer was extracted with toluene (2×200 mL). The organic layers were combined, washed with brine (200 mL), and concentrated to yield 4-(4-isopropyl-piperazine-1-carbonyl)-benzaldehyde (52.5 g, mass balance 101%) as a pale, yellow-brown oil. The oil was dissolved in EtOH (600 mL) and, with vigorous mechanical agitation, was treated with a solution of NaHSO3 (23.1 g, 222 mmol) in de-ionized H2O (50 mL) which was added via an addition funnel over 30 min. The resulting mixture was stirred at room temperature for 48 h, and then cooled to 0° C. Methyl-tert-butyl ether (500 mL) was added and the resulting the slurry was stirred for 30 min. The precipitate was collected by suction filtration through a medium porosity glass frit, washed with cold EtOH/EtOAc (5:1, 3×60 mL). The solids were dried under vacuum for 2 h, then at 40° C. in a vacuum oven for 16 h to yield the title compound as a white solid.

Fuente