1-(3-broMo-5-fluorobenzyl)-4-Methylpiperazine synthesis

Yield:1428065-36-4 51%

Reaction Conditions:

Stage #1: 1-methyl-piperazine;3-bromo-5-fluorobenzaldehydewith acetic acid in methanol at 20; pH=6; for 1 h;
Stage #2: with methanol;sodium cyanoborohydride at 20;

Steps:

1

A solution of 3-bromo-5-fluorobenzaldehyde (CI) (2.12 g, 10.42 mmol) in MeOH (200 mL) was added 1-methylpiperazine (2.3 mL, 20.84 mL). The pH was adjusted to 6 using HOAc and stirred for 1 h. NaCNBH₃ (917 mg, 14.59 mmol) was added and stirred at room temperature overnight. The MeOH was removed under vacuum and the residue was partitioned between CHCl₃ and saturated aqueous NaHCO₃. The organic layer was dried over MgSO₄ and evaporated under vacuum. The crude product was purified on a silica gel column (100% CHCl₃→3:97 MeOH[7N NH₃]:CHCl₃) to produce 1-(3-bromo-5-fluorobenzyl)-4-methylpiperazine (CII) as a yellow oil (1.52 g, 5.29 mmol, 51% yield). ¹H NMR (DMSO-d₆, 500 MHz) δ ppm 2.14 (s, 3H), 2.28-2.40 (m, 8H), 3.46 (s, 2H), 7.15-7.17 (m, 1H), 7.35 (s, 1H), 7.40-7.42 (m, 1H); ESIMS found C₁₂H₁₆BrFN₂ m/z 287 (M+H).

References:

US2013/296302,2013,A1 Location in patent:Paragraph 0598