Acetonitrile → 4-[{N-(2-amino-5-trifluoromethoxybenzoyl) glycyl}aminomethyl]-1-(4-bromobenzyl)piperidine

Temperature

60 °C

A mixture of 4-[{N-(2-(tert-butoxycarbonylamino)-5-trifluoromethoxybenzoyl)glycyl}aminomethyl]piperidine (0.050 mmol), 4-bromobenzyl bromide (0.060 mmol), piperidinomethylpolystyrene (60 mg), acetonitrile (0.8 mL) and chloroform (0.5 mL) was stirred at 60° C. for 12 h. The reaction mixture was cooled, loaded onto Varian™ SCX column and washed with 50% CHCl3/CH3OH (10 mL) and CH3OH (10 mL). Product was eluted using 2 N NH3 in CH3OH (5 mL) and concentrated. To the resulting material was added 4 N HCl in 1,4-dioxane (2 mL), and the solution was stirred overnight at room temperature. Concentration and preparative TLC afforded 4-[{N-(2-amino-5-trifluoromethoxybenzoyl)glycyl}aminomethyl]-1-(4-bromobenzyl)piperidine (Compound No. 1910) (6.5 mg, 24%): The purity was determined by RPLC/MS (96%); ESI/MS m/e 545 (M++H, C23H26BrF3N4O3).

1. temperatureThe reaction mixture was cooled
2. washwashed with 50% CHCl3/CH3OH (10 mL) and CH3OH (10 mL)
3. washProduct was eluted
4. concentrationconcentrated
5. additionTo the resulting material was added 4 N HCl in 1,4-dioxane (2 mL)
6. stirringthe solution was stirred overnight at room temperature
7. concentrationConcentration and preparative TLC

ORD record

ord-1be7cfb436504a7cb43a0b3d56bc0cc4

Source dataset

uspto-grants-2002_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06362177B1