1,4-Dioxane hydrochloride → 4-{2-[(3,5-Dichlorobenzyl)-(5'-isopropyl-2'-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-amino]-pyrimidin-5-yloxy}-butyric acid

HRID 604150Notes

Reaction equation

HRID 604150 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:46]=[C:47]([Cl:49])[CH:48]=1)[CH2:5][N:6]([CH2:24][C:25]1[CH:30]=[C:29]([C:31]([F:34])([F:33])[F:32])[CH:28]=[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:7]1[N:12]=[CH:11][C:10]([O:13][CH2:14][CH2:15][CH2:16][C:17]([O:19]C(C)(C)C)=[O:18])=[CH:9][N:8]=1.Cl.O1CCOCC1>[Cl-].[Na+].O>[Cl:1][C:2]1[CH:3]=[C:4]([CH:46]=[C:47]([Cl:49])[CH:48]=1)[CH2:5][N:6]([CH2:24][C:25]1[CH:30]=[C:29]([C:31]([F:32])([F:33])[F:34])[CH:28]=[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:7]1[N:8]=[CH:9][C:10]([O:13][CH2:14][CH2:15][CH2:16][C:17]([OH:19])=[O:18])=[CH:11][N:12]=1

Participants

4

Reactant 2

HCID 204431481,4-Dioxane hydrochlorideHCID 66603221Tert-butyl 4-{2-[(3,5-dichloro-benzyl)-(5'-isopropyl-2'-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-amino]-pyrimidin-5-yloxy}-butyrate

Product 1

HCID 236419504-{2-[(3,5-Dichlorobenzyl)-(5'-isopropyl-2'-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-amino]-pyrimidin-5-yloxy}-butyric acidYield 82%

Reagents, catalysts & solvents 1

HCID 57417360Sodium chloride; waterSolvent

Procedure

To tert-butyl 4-{2-[(3,5-dichloro-benzyl)-(5′-isopropyl-2′-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-amino]-pyrimidin-5-yloxy}-butyrate (180 mg) is added 4N-hydrochloric acid/dioxane solution (2 ml) and the mixture is stirred at room temperature for 4 hours. To the reaction mixture is added a saturated brine, 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=1:0→19:1) to give 4-{2-[(3,5-dichlorobenzyl)-(5′-isopropyl-2′-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-amino]-pyrimidin-5-yloxy}-butyric acid (136 mg). MS (m/z): 664/662 [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=1:0→19:1)

Sources & evidence

ORD record
ord-36fea743a61f4347b821050ee10a6ad5
Source dataset
uspto-grants-2011_03
Patent number
US07906517B2

Reaction notes

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