Potassium Carbonate → Ethyl 4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)benzoate

HRID 1038664Notes

Reaction equation

HRID 1038664 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:15][C:16]1[CH:26]=[CH:25][C:19]([C:20]([O:22][CH2:23][CH3:24])=[O:21])=[CH:18][C:17]=1[C:27]([F:30])([F:29])[F:28]>O1CCCC1>[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([CH2:15][C:16]2[CH:26]=[CH:25][C:19]([C:20]([O:22][CH2:23][CH3:24])=[O:21])=[CH:18][C:17]=2[C:27]([F:28])([F:30])[F:29])[CH2:4][CH2:3]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 531671-MethylpiperazineHCID 23073576Ethyl 4-(bromomethyl)-3-(trifluoromethyl)benzoate

Product 1

HCID 23145917Ethyl 4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)benzoate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of N-methylpiperazine (5.8 g, 57.9 mmol, 1.0 eq.) in tetrahydrofuran (225 ml) containing anhydrous finely ground potassium carbonate (10.4 g, 75.2 mmol, 1.3 eq.) is added a solution of ethyl 4-bromomethyl-3-trifluoromethylbenzoate (18.0 g, 57.9 mmol, 1.0 eq.) in tetrahydrofuran with vigorous mechanical stirring within 20 min. Stirring is continued at room temperature for 20 h. The obtained suspension is filtered, and the filtrate is evaporated to give a brown oil. The crude product is purified by medium pressure chromatography (290 g silica gel, gradient: TBME to EtOH/TBME 1:4 within 30 min, then 25% NH3/EtOH/TBME 1:19:80 for 60 min). The fractions containing the title compound are pooled and evaporated to afford a yellow oil: HPLC: tR=4.75 min (purity: >99%, gradient A), ESI-MS: 331.4 [MH]+.

Workup

  1. stirringStirring
  2. waitis continued at room temperature for 20 h
  3. filtrationThe obtained suspension is filtered
  4. customthe filtrate is evaporated
  5. customto give a brown oil
  6. customThe crude product is purified by medium pressure chromatography (290 g silica gel, gradient
  7. waitTBME to EtOH/TBME 1:4 within 30 min
  8. wait25% NH3/EtOH/TBME 1:19:80 for 60 min)
  9. additionThe fractions containing the title compound
  10. customevaporated
  11. customto afford a yellow oil

Sources & evidence

ORD record
ord-5486b6d368534f5b9fddae83d59178fd
Source dataset
uspto-grants-2013_10
Patent number
US08552002B2

Reaction notes

Loading…