p-Aminoacetophenone → 1-(4-Amino-3-bromo-phenyl)-ethanone

A mixture containing 48.86 g of p-aminoacetophenone in 490 ml of toluene is stirred while 64.5 g of N-bromosuccinimide is added in portions over 0.5 hours at below 40° C. After 15 minutes, the mixture is washed with H2O (4×100 ml). The solution is dried (MgSO4) and evaporated to dryness to afford 70.53 g of 4-amino-3-bromoacetophenone, mp 59°-62° C. A 35 g sample of this material in 180 ml of dry dimethylformamide is stirred and heated at reflux with 17.57 g of Cu2 (CN)2 for 6 hours under N2 atmosphere. Subsequently, 180 ml of FeCl3 /HCl solution (40 g FeCl3.6H2O/10 ml concentrated HCl/60 ml H2) is added and the mixture is heated for 20 minutes at 60°-70° C. and poured into 350 ml of H2O. The aqueous mixture is extracted with CH2Cl2 and the extracts are washed with H2O, saturated NaHCO3 solution and H2O, respectively. The CH2Cl2 solution is evaporated to dryness in vacuo and the residue is recrystallized from 95% EtOH to afford 14.25 g, mp 155°-159° C., of 4-amino-3-cyanoacetophenone. A 4.8 g sample of this product in 100 ml of EtOAc and 100 ml of CHCl3 containing 13.32 g of CuBr2 is heated at reflux temperature for 20 minutes. The mixture is further heated after 20 ml of EtOH is added and then filtered while still hot. The filter cake is washed with 50 ml of hot 20% MeOH/CH2Cl2 and the combined organic solutions are evaporated to dryness in vacuo. The residue is stirred in 25 ml of CH2Cl2 and the solid is collected and washed with CH2CL2 to give 8.08 g of the phenacyl bromide. This material is added to 50 ml of t-BuNH2 in 100 ml of EtOH at 5° under N2 atmosphere. After 10 minutes of stirring, the mixture is allowed to warm to 30° C. to give a solution. This solution is cooled to 10° and 4 g of NaBH4 is added in portions. After 45 minutes, the mixture is allowed to warm (42° C.) and kept at 20° C. until the exotherm subsides. The mixture is then evaporated to dryness and the residue is washed with H2O. The residue is dried and treated with 200 ml of boiling MeOH and the hot MeOH solution is filtered. The filter cake is further washed with hot MeOH and the combined filtrates are concentrated to afford crystals. This solid is recrystallized from MeOH/2-PrOH to afford 2.08 g, mp 184°-186° C., of the title compound.

1. additionis added in portions over 0.5 hours at below 40° C
2. washthe mixture is washed with H2O (4×100 ml)
3. dry with materialThe solution is dried (MgSO4)
4. customevaporated to dryness

ORD record

ord-bd74d8bef594400d82d40c9598b71812

Source dataset

uspto-grants-1983_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04404222