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

HRID 1640334

Reaction equation

HRID 1640334 reaction equation
[NH:1]1[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.C([O-])([O-])=O.[K+].[K+].[F:13][C:14]1[CH:19]=[CH:18][C:17]([CH:20]([C:27]2[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=2)[O:21][CH2:22][CH2:23][CH2:24][CH2:25]Cl)=[CH:16][CH:15]=1.C(OCC)(=O)C>CN(C=O)C>[F:13][C:14]1[CH:19]=[CH:18][C:17]([CH:20]([C:27]2[CH:28]=[CH:29][C:30]([F:33])=[CH:31][CH:32]=2)[O:21][CH:22]([N:1]2[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]2)[CH2:23][CH2:24][CH3:25])=[CH:16][CH:15]=1

Participants

6

Reactant 4

HCID 4837PiperazineHCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 107573721-[Bis(4-fluorophenyl)methoxy]-4-chlorobutane

Product 1

HCID 667388261-[1-[Bis(4-fluorophenyl)methoxy]butyl]piperazineYield 30%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

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 Ore 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.

Workup

  1. customThe turbid reaction Ore
  2. washwashed
  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)

Sources & evidence

ORD record
ord-a5072b0b32084764b708de00394f8f43
Source dataset
uspto-grants-2012_02
Patent number
US08114379B2

Linked notes

Loading…