Trifluoroacetic acid → 1-{4-[3-(2-Methylpiperidin-1-yl)propoxy]phenyl}piperazine

HRID 1434589Notes

Reaction equation

HRID 1434589 reaction equation
[CH3:1][CH:2]1[CH2:7][CH2:6][CH2:5][CH2:4][N:3]1[CH2:8][CH2:9][CH2:10][O:11][C:12]1[CH:17]=[CH:16][C:15]([N:18]2[CH2:23][CH2:22][N:21](C(OC(C)(C)C)=O)[CH2:20][CH2:19]2)=[CH:14][CH:13]=1.FC(F)(F)C(O)=O.C(=O)(O)[O-].[Na+]>ClCCl>[CH3:1][CH:2]1[CH2:7][CH2:6][CH2:5][CH2:4][N:3]1[CH2:8][CH2:9][CH2:10][O:11][C:12]1[CH:17]=[CH:16][C:15]([N:18]2[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]2)=[CH:14][CH:13]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 579358121,1-Dimethylethyl 4-(4-{[3-(2-methyl-1-piperidinyl)propyl]oxy}phenyl)-1-piperazinecarboxylate

Product 1

HCID 579358411-{4-[3-(2-Methylpiperidin-1-yl)propoxy]phenyl}piperazineYield 74.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

1,1-Dimethylethyl 4-(4-{[3-(2-methyl-1-piperidinyl) propyl]oxy}phenyl)-1-piperazinecarboxylate (E76a) (1.66 g) was dissolved in dry dichloromethane (25 ml) and stirred under nitrogen. 50% Trifluoroacetic acid in dichloromethane (5 ml) was added, and the mixture was stirred at room temperature for 4 h. Saturated sodium bicarbonate solution was then added and the mixture was extracted with dichloromethane. The organic phase was separated using a hydrophobic frit, and evaporated in vacuo, however, most of the product was in the aqueous phase. The product was removed from the aqueous phase using an OASIS cartridge, washing with water and eluting with methanol, and further purified using an aminopropyl bond elut cartridge, eluting with dichloromethane and then SCX cartridge, eluting with 50% [0.880 ammonia-methanol (1:9)]-dichloromethane to give the title compound (0.94 g). LCMS RT=1.01 min, ES+ve m/z=318 (M+H)+

Workup

  1. stirringthe mixture was stirred at room temperature for 4 h
  2. extractionthe mixture was extracted with dichloromethane
  3. customThe organic phase was separated
  4. customevaporated in vacuo
  5. customThe product was removed from the aqueous phase
  6. washwashing with water
  7. washeluting with methanol
  8. customfurther purified
  9. washeluting with dichloromethane
  10. washSCX cartridge, eluting with 50% [0.880 ammonia-methanol (1:9)]-dichloromethane

Sources & evidence

ORD record
ord-237423a2ff61401ba24f64c59fcc0e2a
Source dataset
uspto-grants-2009_11
Patent number
US07615550B2

Reaction notes

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