Citric Acid → 4-(2-{2-[(3,5-Bis-trifluoromethyl-benzyl)-ethyl-amino]-5-trifluoromethyl-benzylamino}-pyrimidin-5-yloxy)-butyric acid

HRID 604099Notes

Reaction equation

HRID 604099 reaction equation
[F:1][C:2]([F:47])([F:46])[C:3]1[CH:4]=[C:5]([CH:39]=[C:40]([C:42]([F:45])([F:44])[F:43])[CH:41]=1)[CH2:6][N:7]([CH2:37][CH3:38])[C:8]1[CH:32]=[CH:31][C:30]([C:33]([F:36])([F:35])[F:34])=[CH:29][C:9]=1[CH2:10][NH:11][C:12]1[N:17]=[CH:16][C:15]([O:18][CH2:19][CH2:20][CH2:21][C:22]([O:24]C(C)(C)C)=[O:23])=[CH:14][N:13]=1.Cl.C(=O)(O)[O-].[Na+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>O1CCOCC1>[F:45][C:42]([F:43])([F:44])[C:40]1[CH:39]=[C:5]([CH:4]=[C:3]([C:2]([F:1])([F:46])[F:47])[CH:41]=1)[CH2:6][N:7]([CH2:37][CH3:38])[C:8]1[CH:32]=[CH:31][C:30]([C:33]([F:35])([F:36])[F:34])=[CH:29][C:9]=1[CH2:10][NH:11][C:12]1[N:13]=[CH:14][C:15]([O:18][CH2:19][CH2:20][CH2:21][C:22]([OH:24])=[O:23])=[CH:16][N:17]=1

Participants

6

Reactant 4

HCID 311Citric AcidHCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 86626851Tert-butyl 4-(2-{2-[(3,5-bis-trifluoromethyl-benzyl)-ethyl-amino]-5-trifluoromethyl-benzylamino}-pyrimidin-5-yloxy)-butyrate

Product 1

HCID 575560484-(2-{2-[(3,5-Bis-trifluoromethyl-benzyl)-ethyl-amino]-5-trifluoromethyl-benzylamino}-pyrimidin-5-yloxy)-butyric acidYield 61%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To tert-butyl 4-(2-{2-[(3,5-bis-trifluoromethyl-benzyl)-ethyl-amino]-5-trifluoromethyl-benzylamino}-pyrimidin-5-yloxy)-butyrate (84 mg) is added a 4N-hydrochloric acid in dioxane (1.5 ml), and the mixture is stirred at room temperature for 1 hour. The reaction mixture is neutralized with a saturated aqueous sodium bicarbonate solution and made weakly acidic with 10% aqueous citric acid solution, and the mixture is extracted with ethyl acetate. The organic layer is washed with a saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue is purified by silica gel column chromatography (chloroform:methanol=19:1) to give 4-(2-{2-[(3,5-bis-trifluoromethyl-benzyl)-ethyl-amino]-5-trifluoromethyl-benzylamino}-pyrimidin-5-yloxy)-butyric acid (47 mg). MS (m/z): 625 [M+H]+

Workup

  1. extractionthe mixture is extracted with ethyl acetate
  2. washThe organic layer is washed with a saturated brine
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting residue is purified by silica gel column chromatography (chloroform:methanol=19:1)

Sources & evidence

ORD record
ord-36263df32258413a90c460ad1c7e2e26
Source dataset
uspto-grants-2011_03
Patent number
US07906517B2

Reaction notes

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