Sodium Hydroxide → 2-[(3,5-Bis-trifluoromethyl-benzyl)-(5'-isopropyl-2'-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-amino]-pyrimidine-5-carboxylic acid

HRID 604122Notes

Reaction equation

HRID 604122 reaction equation
[F:1][C:2]([F:49])([F:48])[C:3]1[CH:4]=[C:5]([CH:41]=[C:42]([C:44]([F:47])([F:46])[F:45])[CH:43]=1)[CH2:6][N:7]([CH2:19][C:20]1[CH:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:23]=[CH:22][C:21]=1[C:30]1[CH:35]=[C:34]([CH:36]([CH3:38])[CH3:37])[CH:33]=[CH:32][C:31]=1[O:39][CH3:40])[C:8]1[N:13]=[CH:12][C:11]([C:14]([O:16]CC)=[O:15])=[CH:10][N:9]=1.[OH-].[Na+]>C(O)C.O1CCCC1>[F:47][C:44]([F:45])([F:46])[C:42]1[CH:41]=[C:5]([CH:4]=[C:3]([C:2]([F:1])([F:48])[F:49])[CH:43]=1)[CH2:6][N:7]([CH2:19][C:20]1[CH:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:23]=[CH:22][C:21]=1[C:30]1[CH:35]=[C:34]([CH:36]([CH3:37])[CH3:38])[CH:33]=[CH:32][C:31]=1[O:39][CH3:40])[C:8]1[N:9]=[CH:10][C:11]([C:14]([OH:16])=[O:15])=[CH:12][N:13]=1

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 86626869Ethyl 2-[(3,5-bis-trifluoromethyl-benzyl)-(5'-isopropyl-2'-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-amino]-pyrimidine-5-carboxylate

Product 1

HCID 866268702-[(3,5-Bis-trifluoromethyl-benzyl)-(5'-isopropyl-2'-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-amino]-pyrimidine-5-carboxylic acidYield 66.3%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

Ethyl 2-[(3,5-bis-trifluoromethyl-benzyl)-(5′-isopropyl-2′-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-amino]-pyrimidine-5-carboxylate (1.1 g) is dissolved in a mixed solvent of ethanol (18 ml) and tetrahydrofuran (20 ml) and thereto is added a 2M-aqueous sodium hydroxide solution (3 ml), and the mixture is stirred at 50° C. for 1 hour and a half. The reaction solution is concentrated under reduced pressure and thereto is added a 1N-hydrochloric acid 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=25:1) to give 2-[(3,5-bis-trifluoromethyl-benzyl)-(5′-isopropyl-2′-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-amino]-pyrimidine-5-carboxylic acid (700 mg). MS (m/z): 672 [M+H]+

Workup

  1. concentrationThe reaction solution is concentrated under reduced pressure
  2. additionis added a 1N-hydrochloric acid
  3. extractionthe mixture is extracted with ethyl acetate
  4. washThe organic layer is washed with a saturated brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting residue is purified by silica gel column chromatography (chloroform:methanol=25:1)

Sources & evidence

ORD record
ord-d253a5bcd42f4fc9ac474c1e01d41b76
Source dataset
uspto-grants-2011_03
Patent number
US07906517B2

Reaction notes

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