Piperazine → 1-[1-[Bis(4-fluorophenyl)methoxy]butyl]piperazine

Piperazine (4.31 g, 50 mmol) was dissolved in 40 mL of anhydrous DMF and stirred with K2CO3 powder (2.76 g, 20 mmol) and KI (100 mg, 0.6 mmol) for 0.5 h. To this turbid solution, 1-[bis(4-fluorophenyl)methoxy]-4-chlorobutane (2, 1.55 g, 5 mmol) in 10 mL of DMF was added slowly. The reaction mixture was stirred for 72 h at 60°-70°. The turbid reaction mixture was poured into 200 mL of ethyl acetate, washed with sat. NaCl solution (60 mL×5), dried over MgSO4 and evaporated to dryness. The crude oil was applied to a silica gel column for purification. Elution with CHCl3:MeOH (93:7) afforded the desired mono-alkylated product 3 (540 mg, 1.5 mmol, 30%) as a slightly yellow oil. 1H NMR (CDCl3): δ 1.55-1.69 (4H, m), 2.31 (2H, t, J=7.5), 2.39 (4H, br s), 2.88 (4H, t, J=4.8), 3.43 (2H, t, J=6.0), 5.28 (1H, s), 6.98-7.02 (4H, m), 7.25-7.29 (4H, m). mp (bis oxalate salt): 215°-218° C. Anal. C25H30N2O9F2) C, H, N.

1. customThe turbid reaction mixture
2. washwashed with sat. NaCl solution (60 mL×5)
3. dry with materialdried over MgSO4
4. customevaporated to dryness
5. customThe crude oil was applied to a silica gel column for purification
6. washElution with CHCl3:MeOH (93:7)

ORD-Eintrag

ord-a90baf96b57f4904a41c9f37ca32d099

Quelldatensatz

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08772319B2