Trifluoroacetic acid → 3-Methyl-2-[4-(4-pyridin-3-yl-phenyl)piperazine-1-sulfonylmethyl]butyric acid

HRID 393693Notes

Reaction equation

HRID 393693 reaction equation
C([O:5][C:6](=[O:16])[CH:7]([CH2:11][S:12](Cl)(=[O:14])=[O:13])[CH:8]([CH3:10])[CH3:9])(C)(C)C.[N:17]1[CH:22]=[CH:21][CH:20]=[C:19]([C:23]2[CH:28]=[CH:27][C:26]([N:29]3[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]3)=[CH:25][CH:24]=2)[CH:18]=1.C(N(CC)CC)C.FC(F)(F)C(O)=O>ClCCl>[CH3:10][CH:8]([CH3:9])[CH:7]([CH2:11][S:12]([N:32]1[CH2:33][CH2:34][N:29]([C:26]2[CH:25]=[CH:24][C:23]([C:19]3[CH:18]=[N:17][CH:22]=[CH:21][CH:20]=3)=[CH:28][CH:27]=2)[CH2:30][CH2:31]1)(=[O:13])=[O:14])[C:6]([OH:5])=[O:16]

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 212590942-Chlorosulfonylmethyl-3-methyl-butyric acid tert-butyl esterHCID 226466841-(4-Pyridin-3-yl-phenyl)piperazine

Product 1

HCID 226467343-Methyl-2-[4-(4-pyridin-3-yl-phenyl)piperazine-1-sulfonylmethyl]butyric acidYield 93%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-Chlorosulfonylmethyl-3-methylbutyric acid tert-butyl ester (0.072 g) [preparation described in WO-A-98/05635] was added as a solution in dichloromethane (2 ml) to a stirred mixture of 1-(4-pyridin-3-yl-phenyl)piperazine (0.053 g) and triethylamine (40 μl) and the resultant solution stirred at room temperature for 2 h. Trifluoroacetic acid (4 ml) was then added dropwise, and the mixture stirred for a further 2 h. The solvent were removed under reduced pressure and the residue azeotroped with 1:1 dichloromethane/hexane (2×10 ml). The residue was then diluted with diethyl ether (20 ml) and extracted with 1 M sodium hydroxide (10 ml) followed by 0.5 M sodium hydroxide (10 ml). The combined aqueous extracts were then washed with diethyl ether (20 ml), then cautiously acidified to pH 5 with acetic acid, forming a precipitate. The mixture was then extracted with ethyl acetate (3×20 ml). The combined organic extracts were washed with water (2×10 ml), saturated brine (10 ml), dried (Na2SO4) and reduced in vacuo to give the title compound as a pale green solid (0.085 g, 93%).

Workup

  1. customThe solvent were removed under reduced pressure
  2. customthe residue azeotroped with 1:1 dichloromethane/hexane (2×10 ml)
  3. additionThe residue was then diluted with diethyl ether (20 ml)
  4. extractionextracted with 1 M sodium hydroxide (10 ml)
  5. washThe combined aqueous extracts were then washed with diethyl ether (20 ml)
  6. customforming a precipitate
  7. extractionThe mixture was then extracted with ethyl acetate (3×20 ml)
  8. washThe combined organic extracts were washed with water (2×10 ml), saturated brine (10 ml)
  9. dry with materialdried (Na2SO4)

Sources & evidence

ORD record
ord-3129ce0f2846458e9498dd75f4f985db
Source dataset
uspto-grants-2004_10
Patent number
US06809100B2

Reaction notes

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