Sodium Hydroxide → (S)-3-Methyl-1-((4-(trifluoromethyl)phenyl)sulfonyl)piperazine

HRID 2365447Notes

Reaction equation

HRID 2365447 reaction equation
[CH3:1][C@H:2]1[CH2:7][NH:6][CH2:5][CH2:4][NH:3]1.[OH-].[Na+].[F:10][C:11]([F:23])([F:22])[C:12]1[CH:17]=[CH:16][C:15]([S:18](Cl)(=[O:20])=[O:19])=[CH:14][CH:13]=1>O1CCCC1.C(Cl)Cl.O.FC(F)(F)C1C=CC(S(Cl)(=O)=O)=CC=1>[CH3:1][C@@H:2]1[NH:3][CH2:4][CH2:5][N:6]([S:18]([C:15]2[CH:14]=[CH:13][C:12]([C:11]([F:10])([F:22])[F:23])=[CH:17][CH:16]=2)(=[O:20])=[O:19])[CH2:7]1

Participants

8

Reactant 3

HCID 14798Sodium HydroxideHCID 27342192-Methylpiperazine, (S)-HCID 27773994-(Trifluoromethyl)benzenesulfonyl chloride

Product 1

HCID 59152086(S)-3-Methyl-1-((4-(trifluoromethyl)phenyl)sulfonyl)piperazineYield 64.9%

Reagents, catalysts & solvents 4

HCID 27773994-(Trifluoromethyl)benzenesulfonyl chlorideCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

(2S)-2-Methylpiperazine (15 g, 150 mmol) was dissolved in tetrahydrofuran (300 mL) and the solution was cooled down to 0° C. Sodium hydroxide (150 mL, 449 mmol) was added, then 4-(trifluoromethyl)benzenesulfonyl chloride (40 g, 164 mmol) (dissolved in 200 ml THF) was added dropwise and the resulting mixture was stirred for 1 h. Further 4-(trifluoromethyl)benzenesulfonyl chloride (0.06 eq, 2.2 g) was added and mixture stirred for 10 min. The mixture was diluted with DCM (500 ml) and water (500 ml) and stirred for 5 min. The phases were separated, the aqueous layer was extracted with DCM (1000 ml) and the organic phases concentrated under reduced pressure. The residue was taken-up with 1 M HCl (500 ml) and washed with DCM in order to extracted impurities. The aqueous phase was basified to pH=9 with NaOH 3M, extracted with DCM (3×500 ml) and the combined organic phases dried over Na2SO4 before the solvent was removed under reduced pressure to give the title compound (30 g).

Workup

  1. stirringmixture stirred for 10 min
  2. stirringstirred for 5 min
  3. customThe phases were separated
  4. extractionthe aqueous layer was extracted with DCM (1000 ml)
  5. concentrationthe organic phases concentrated under reduced pressure
  6. washwashed with DCM in order
  7. extractionto extracted impurities
  8. extractionextracted with DCM (3×500 ml)
  9. dry with materialthe combined organic phases dried over Na2SO4 before the solvent
  10. customwas removed under reduced pressure

Sources & evidence

ORD record
ord-9d66651c46af41c995d88841c2da6eca
Source dataset
uspto-grants-2014_04
Patent number
US08697703B2

Reaction notes

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