Citric Acid → 5-[(2-{[(3,5-Bis-trifluoromethyl-benzyl)-(5-morpholin-4-yl-pyrimidin-2-yl)-amino]-methyl}-4-trifluoromethyl-phenyl)-ethoxycarbonyl-amino]-pentanoic acid

HRID 604050Notes

Reaction equation

HRID 604050 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]([CH2:20][C:21]1[CH:26]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:24]=[CH:23][C:22]=1[N:31]([C:41]([O:43][CH2:44][CH3:45])=[O:42])[CH2:32][CH2:33][CH2:34][CH2:35][C:36]([O:38]CC)=[O:37])[C:8]1[N:13]=[CH:12][C:11]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)=[CH:10][N:9]=1.[OH-].[Na+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CO>[F:52][C:49]([F:50])([F:51])[C:47]1[CH:46]=[C:5]([CH:4]=[C:3]([C:2]([F:53])([F:1])[F:54])[CH:48]=1)[CH2:6][N:7]([CH2:20][C:21]1[CH:26]=[C:25]([C:27]([F:28])([F:29])[F:30])[CH:24]=[CH:23][C:22]=1[N:31]([C:41]([O:43][CH2:44][CH3:45])=[O:42])[CH2:32][CH2:33][CH2:34][CH2:35][C:36]([OH:38])=[O:37])[C:8]1[N:13]=[CH:12][C:11]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)=[CH:10][N:9]=1

Participants

5

Reactant 3

HCID 311Citric AcidHCID 14798Sodium HydroxideHCID 86626805Ethyl 5-[(2-{[(3,5-bis-trifluoromethyl-benzyl)-(5-morpholin-4-yl-pyrimidin-2-yl)-amino]-methyl}-4-trifluoromethyl-phenyl)-ethoxycarbonyl-amino]-pentanoate

Product 1

HCID 866268065-[(2-{[(3,5-Bis-trifluoromethyl-benzyl)-(5-morpholin-4-yl-pyrimidin-2-yl)-amino]-methyl}-4-trifluoromethyl-phenyl)-ethoxycarbonyl-amino]-pentanoic acidYield 95.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Ethyl 5-[(2-{[(3,5-bis-trifluoromethyl-benzyl)-(5-morpholin-4-yl-pyrimidin-2-yl)-amino]-methyl}-4-trifluoromethyl-phenyl)-ethoxycarbonyl-amino]-pentanoate (134 mg) is dissolved in methanol (1 ml), and thereto is added 1M-aqueous sodium hydroxide solution (1 ml), and the mixture is stirred at room temperature for 1 hour and a half. The reaction solution is made weakly acidic with a 10% aqueous citric acid solution, and the mixture is extracted with ethyl acetate, 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=19:1) to give 5-[(2-{[(3,5-bis-trifluoromethyl-benzyl)-(5-morpholin-4-yl-pyrimidin-2-yl)-amino]-methyl}-4-trifluoromethyl-phenyl)-ethoxycarbonyl-amino]-pentanoic acid (123 mg). MS (m/z): 752 [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-0b2a6da1defd4a1ab06c090b076ba3fe
Source dataset
uspto-grants-2011_03
Patent number
US07906517B2

Reaction notes

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