Citric Acid → 3-{2-[(3,5-Bis-trifluoromethyl-benzyl)-(5'-isopropyl-4,5,2'-trimethoxy-biphenyl-2-ylmethyl)-amino]-pyrimidin-5-yloxy}-propionic acid sodium salt

HRID 604180Notes

Reaction equation

HRID 604180 reaction equation
[F:1][C:2]([F:54])([F:53])[C:3]1[CH:4]=[C:5]([CH:46]=[C:47]([C:49]([F:52])([F:51])[F:50])[CH:48]=1)[CH2:6][N:7]([CH2:24][C:25]1[CH:30]=[C:29]([O:31][CH3:32])[C:28]([O:33][CH3:34])=[CH:27][C:26]=1[C:35]1[CH:40]=[C:39]([CH:41]([CH3:43])[CH3:42])[CH:38]=[CH:37][C:36]=1[O:44][CH3:45])[C:8]1[N:13]=[CH:12][C:11]([O:14][CH2:15][CH2:16][C:17]([O:19]C(C)(C)C)=[O:18])=[CH:10][N:9]=1.Cl.O1CCOCC1.C(=O)(O)[O-].[Na+:66].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>>[Na+:66].[F:54][C:2]([F:1])([F:53])[C:3]1[CH:4]=[C:5]([CH:46]=[C:47]([C:49]([F:50])([F:51])[F:52])[CH:48]=1)[CH2:6][N:7]([CH2:24][C:25]1[CH:30]=[C:29]([O:31][CH3:32])[C:28]([O:33][CH3:34])=[CH:27][C:26]=1[C:35]1[CH:40]=[C:39]([CH:41]([CH3:43])[CH3:42])[CH:38]=[CH:37][C:36]=1[O:44][CH3:45])[C:8]1[N:9]=[CH:10][C:11]([O:14][CH2:15][CH2:16][C:17]([O-:19])=[O:18])=[CH:12][N:13]=1

Participants

5

Reactant 4

HCID 311Citric AcidHCID 516892Sodium BicarbonateHCID 204431481,4-Dioxane hydrochlorideHCID 86626910Tert-butyl 3-{2-[(3,5-bis-trifluoromethyl-benzyl)-(5'-isopropyl-4,5,2'-trimethoxy-biphenyl-2-ylmethyl)-amino]-pyrimidin-5-yloxy}-propionate

Product 1

HCID 237127253-{2-[(3,5-Bis-trifluoromethyl-benzyl)-(5'-isopropyl-4,5,2'-trimethoxy-biphenyl-2-ylmethyl)-amino]-pyrimidin-5-yloxy}-propionic acid sodium salt

Procedure

To tert-butyl 3-{2-[(3,5-bis-trifluoromethyl-benzyl)-(5′-isopropyl-4,5,2′-trimethoxy-biphenyl-2-ylmethyl)-amino]-pyrimidin-5-yloxy}-propionate (41 mg) is added a 4N-hydrochloric acid/dioxane (4 ml) and the mixture is stirred at room temperature for 9 hours. The reaction mixture is neutralized with a saturated aqueous sodium bicarbonate solution and the mixture is made weakly acidic with a 10% aqueous citric acid solution, and 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 (hexane:ethyl acetate=4:1→1:3) and the resulting purified product is dissolved in ethanol (0.5 ml) and thereto is added 1M-aqueous sodium hydroxide solution (24 μl) and the mixture is concentrated under reduced pressure to give 3-{2-[(3,5-bis-trifluoromethyl-benzyl)-(5′-isopropyl-4,5,2′-trimethoxy-biphenyl-2-ylmethyl)-amino]-pyrimidin-5-yloxy}-propionic acid sodium salt (18 mg). MS (m/z): 706 [M−Na]−

Workup

  1. extractionextracted 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 (hexane:ethyl acetate=4:1→1:3)
  6. customthe resulting purified product
  7. dissolutionis dissolved in ethanol (0.5 ml)
  8. additionis added 1M-aqueous sodium hydroxide solution (24 μl)
  9. concentrationthe mixture is concentrated under reduced pressure

Sources & evidence

ORD record
ord-b5847a967cdd4b43a2cd02e9fe498f24
Source dataset
uspto-grants-2011_03
Patent number
US07906517B2

Reaction notes

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