Diisopropylethylamine → (3R)-3-methyl-1-[5-(trifluoromethyl)pyridin-2-yl]piperazine

Temperature

140 °C

A suspension of 2-bromo-5-trifluoromethyl-pyridine (2.37 g; 10.0 mmol; 1.0 eq.), (R)-2-methylpiperazine (2.00 g; 20.0 mmol; 2.0 eq.) and DIEA (1.94 g; 15.0 mmol; 1.5 eq.) in 4 mL of DMA was heated at 140° C. for 14 h. The mixture was cooled to room temperature. After evaporation of the solvent under vacuum, the residue was dissolved in a 1/1 mixture of DCM/Et2O. A 4N solution of HCl was added (10 mL) then the resulting precipitate was collected and washed with Et2O. The solid was then poured to an aq. solution of NaOH (5N, 20 mL) and the resulting mixture was extracted with Et2O (3×). The combined organic layers were washed with brine, dried over MgSO4, filtered and evaporated to give the title compound as an orange solid (1680 mg, 69%) used without further purification for the next steps. M+(ESI): 246.3. HPLC (Condition A), Rt: 1.0 min (HPLC purity: 99.9%).

1. temperatureThe mixture was cooled to room temperature
2. customAfter evaporation of the solvent under vacuum
3. dissolutionthe residue was dissolved in a 1/1 mixture of DCM/Et2O
4. additionA 4N solution of HCl was added (10 mL)
5. customthe resulting precipitate was collected
6. washwashed with Et2O
7. additionThe solid was then poured to an aq. solution of NaOH (5N, 20 mL)
8. extractionthe resulting mixture was extracted with Et2O (3×)
9. washThe combined organic layers were washed with brine
10. dry with materialdried over MgSO4
11. filtrationfiltered
12. customevaporated

ORD record

ord-552dda5a4b7a40288f02e4d66c2c74bc

Source dataset

uspto-grants-2011_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08008302B2