Sodium Hydroxide → 4-{2-[(3,5-Bis-trifluoromethyl-benzyl)-(4'-fluoro-5'-isopropyl-4,5,2'-trimethoxy-biphenyl-2-ylmethyl)-amino]-pyrimidin-5-yloxy}-butyric acid

HRID 604169Notes

Reaction equation

HRID 604169 reaction equation
[F:1][C:2]([F:56])([F:55])[C:3]1[CH:4]=[C:5]([CH:48]=[C:49]([C:51]([F:54])([F:53])[F:52])[CH:50]=1)[CH2:6][N:7]([CH2:25][C:26]1[CH:31]=[C:30]([O:32][CH3:33])[C:29]([O:34][CH3:35])=[CH:28][C:27]=1[C:36]1[CH:41]=[C:40]([CH:42]([CH3:44])[CH3:43])[C:39]([F:45])=[CH:38][C:37]=1[O:46][CH3:47])[C:8]1[N:13]=[CH:12][C:11]([O:14][CH2:15][CH2:16][CH2:17][C:18]([O:20]C(C)(C)C)=[O:19])=[CH:10][N:9]=1.Cl.O1CCOCC1.[OH-].[Na+]>C(OCC)(=O)C>[F:55][C:2]([F:1])([F:56])[C:3]1[CH:4]=[C:5]([CH:48]=[C:49]([C:51]([F:52])([F:54])[F:53])[CH:50]=1)[CH2:6][N:7]([CH2:25][C:26]1[CH:31]=[C:30]([O:32][CH3:33])[C:29]([O:34][CH3:35])=[CH:28][C:27]=1[C:36]1[CH:41]=[C:40]([CH:42]([CH3:43])[CH3:44])[C:39]([F:45])=[CH:38][C:37]=1[O:46][CH3:47])[C:8]1[N:13]=[CH:12][C:11]([O:14][CH2:15][CH2:16][CH2:17][C:18]([OH:20])=[O:19])=[CH:10][N:9]=1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 204431481,4-Dioxane hydrochlorideHCID 86626905Tert-butyl 4-{2-[(3,5-bis-trifluoromethyl-benzyl)-(4'-fluoro-5'-isopropyl-4,5,2'-trimethoxy-biphenyl-2-ylmethyl)-amino]-pyrimidin-5-yloxy}-butyrate

Product 1

HCID 866269064-{2-[(3,5-Bis-trifluoromethyl-benzyl)-(4'-fluoro-5'-isopropyl-4,5,2'-trimethoxy-biphenyl-2-ylmethyl)-amino]-pyrimidin-5-yloxy}-butyric acidYield 83.4%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To tert-butyl 4-{2-[(3,5-bis-trifluoromethyl-benzyl)-(4′-fluoro-5′-isopropyl-4,5,2′-trimethoxy-biphenyl-2-ylmethyl)-amino]-pyrimidin-5-yloxy}-butyrate (129 mg) is added a 4N-hydrogen chloride/dioxane solution (3 ml) and the mixture is stirred at room temperature for 7 hours. To the reaction solution are added a saturated aqueous sodium hydroxide solution and ethyl acetate, and the mixture is separated, and 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=1:0→9:1) to give 4-{2-[(3,5-bis-trifluoromethyl-benzyl)-(4′-fluoro-5′-isopropyl-4,5,2′-trimethoxy-biphenyl-2-ylmethyl)-amino]-pyrimidin-5-yloxy}-butyric acid (100 mg). MS (m/z): 740 [M+H]+

Workup

  1. customthe mixture is separated
  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=1:0→9:1)

Sources & evidence

ORD record
ord-27396c84d2aa408bb685c5c3eef775c8
Source dataset
uspto-grants-2011_03
Patent number
US07906517B2

Reaction notes

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