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

HRID 1184847Notes

Reaction equation

HRID 1184847 reaction equation
[CH2:1]([O:3][C:4](=[O:17])[C:5]1[CH:10]=[CH:9][C:8]([CH2:11]Br)=[C:7]([C:13]([F:16])([F:15])[F:14])[CH:6]=1)[CH3:2].C([O-])([O-])=O.[K+].[K+].C[N:25]([CH3:31])[CH:26]1[CH2:30][CH2:29][NH:28][CH2:27]1>C1COCC1.CN(C=O)C.O>[CH2:1]([O:3][C:4](=[O:17])[C:5]1[CH:10]=[CH:9][C:8]([CH2:11][N:28]2[CH2:27][CH2:26][N:25]([CH3:31])[CH2:30][CH2:29]2)=[C:7]([C:13]([F:16])([F:15])[F:14])[CH:6]=1)[CH3:2]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 27585193-(Dimethylamino)pyrrolidineHCID 23073576Ethyl 4-(bromomethyl)-3-(trifluoromethyl)benzoate

Product 1

HCID 23145917Ethyl 4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)benzoateYield 16.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-bromomethyl-3-trifluoromethyl-benzoic acid ethyl ester 36 (120 mg, 0.386 mmol) in THF (4 mL) and DMF (1 mL) was added K2CO3 (80 mg, 0.579 mmol) and 3-(dimethylamino)pyrrolidine (0.043 mL, 38.6 mg, 0.386 mmol). The resulting mixture was stirred at rt for 4 h. The reaction mixture was poured out in water and extracted twice with ethyl acetate. The combined organic extracts were dried, filtered and concentrated in vacuo. The crude material was purified by chromatography CH2Cl2/MeOH (95/5) to give pure 4-(4-methyl-piperazin-1-ylmethyl)-3-trifluoromethyl-benzoic acid ethyl ester 37 (21 mg, 16%).

Workup

  1. extractionextracted twice with ethyl acetate
  2. customThe combined organic extracts were dried
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe crude material was purified by chromatography CH2Cl2/MeOH (95/5)

Sources & evidence

ORD record
ord-c1e17d81f40c4b4f8a3aebf23d094fab
Source dataset
uspto-grants-2014_03
Patent number
US08669256B2

Reaction notes

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