Benzoic acid, 4-fluoro-, ethyl ester → Ethyl 4-((3S,5R)-3,5-dimethylpiperazin-1-yl)benzoate

HRID 16865Notes

Reaction equation

HRID 16865 reaction equation
[CH3:1][C@H:2]1[CH2:7][NH:6][CH2:5][C@@H:4]([CH3:8])[NH:3]1.[CH2:9]([O:11][C:12](=[O:20])[C:13]1[CH:18]=[CH:17][C:16](F)=[CH:15][CH:14]=1)[CH3:10]>CS(C)=O>[CH3:8][C@H:4]1[NH:3][C@@H:2]([CH3:1])[CH2:7][N:6]([C:16]2[CH:17]=[CH:18][C:13]([C:12]([O:11][CH2:9][CH3:10])=[O:20])=[CH:14][CH:15]=2)[CH2:5]1

Participants

4

Reactant 2

HCID 67976Benzoic acid, 4-fluoro-, ethyl esterHCID 6950261rel-(2R,6S)-2,6-dimethylpiperazine

Product 1

HCID 23381002Ethyl 4-((3S,5R)-3,5-dimethylpiperazin-1-yl)benzoateYield 71.9%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
120 °C

Procedure

(2S,6R)-2,6-dimethylpiperazine (6.85 g, 60.00 mmol) was added to ethyl-4-fluorobenzoate (2.20 mL, 15 mmol), in DMSO (40 mL) and warmed to 120° C. under nitrogen. The resulting solution was stirred at 120° C. for 20 h. The reaction mixture was cooled and the solvent evaporated. The crude product was purified by silica column chromatography, eluting with a gradient of 0 to 10% methanol in dichloromethane containing 1% 0.880 ammonia. Pure fractions were evaporated to dryness to afford ethyl 4-((3R,5S)-3,5-dimethylpiperazin-1-yl)benzoate (2.83 g, 71.9%) as a brown oil, which solidified on standing.

Workup

  1. temperatureThe reaction mixture was cooled
  2. customthe solvent evaporated
  3. customThe crude product was purified by silica column chromatography
  4. washeluting with a gradient of 0 to 10% methanol in dichloromethane containing 1% 0.880 ammonia
  5. customPure fractions were evaporated to dryness

Sources & evidence

ORD record
ord-6a5a08e9ca8448a39f05d86d759d82d4
Source dataset
uspto-grants-2010_06
Patent number
US07737149B2

Reaction notes

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