Ethyl Acetate → HCID 86626760, compound

HRID 604000Notes

Reaction equation

HRID 604000 reaction equation
[F:1][C:2]([F:48])([F:47])[C:3]1[CH:4]=[C:5]([CH:40]=[C:41]([C:43]([F:46])([F:45])[F:44])[CH:42]=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[N:30]([CH2:33][CH:34]1[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]1)[CH2:31][CH3:32])[C:8]1[N:13]=[CH:12][C:11]([O:14][CH2:15][CH2:16][CH2:17][OH:18])=[CH:10][N:9]=1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C1=CC=CC=2)=[O:51].C(OCC)(=O)C>C(Cl)Cl>[F:48][C:2]([F:1])([F:47])[C:3]1[CH:4]=[C:5]([CH:40]=[C:41]([C:43]([F:44])([F:45])[F:46])[CH:42]=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[N:30]([CH2:33][CH:34]1[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]1)[CH2:31][CH3:32])[C:8]1[N:9]=[CH:10][C:11]([O:14][CH2:15][CH2:16][C:17]([OH:51])=[O:18])=[CH:12][N:13]=1

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 159087TriacetoxyperiodinaneHCID 86626758HCID 86626758, compound

Product 1

HCID 86626760HCID 86626760, compoundYield 42%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

3-(2-{(3,5-Bis-trifluoromethyl-benzyl)-[2-(cyclohexylmethyl-ethyl-amino)-5-trifluoromethyl-benzyl]-amino}-pyrimidin-5-yloxy)-propan-1-ol (140 mg) is dissolved in methylene chloride (2 ml), and thereto is added 1,1,1-tris(acetyloxy)-1,1-dihydro-1,2-benziodoxol-3-(1H)-one (188 mg) at room temperature and the mixture is stirred at room temperature overnight. Thereto are added ethyl acetate and a saturated brine, 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 dissolved in the mixed solvent of tert-butanol (4 ml) and water (1 ml) and thereto are added 2-methyl-2-butene (128 μl), sodium dihydrogenphosphate dihydrate (44 mg) and sodium chlorite (73 mg) and the mixture is stirred at room temperature for 30 minutes. Thereto are added ethyl acetate and a 1N-hydrochloric acid, 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 (hexane:ethyl acetate=9:1→2:3) to give 3-(2-{(3,5-bis-trifluoromethyl-benzyl)-[2-(cyclohexylmethyl-ethyl-amino)-5-trifluoromethyl-benzyl]-amino}-pyrimidin-5-yloxy)-propionic acid (60 mg). The resulting carboxylic acid is dissolved in ethanol (0.5 ml), and thereto is added 1N-aqueous sodium hydroxide solution (85 μl) and the reaction solution is concentrated under reduced pressure to give 3-(2-{(3,5-bis-trifluoromethyl-benzyl)-[2-(cyclohexylmethyl-ethyl-amino)-5-trifluoromethyl-benzyl]-amino}-pyrimidin-5-yloxy)-propionic acid sodium salt (60 mg). MS (m/z): 705 [M−Na]−.

Workup

  1. customa saturated brine, and the 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. dissolutionThe resulting residue is dissolved in the mixed solvent of tert-butanol (4 ml) and water (1 ml)
  6. additionare added 2-methyl-2-butene (128 μl), sodium dihydrogenphosphate dihydrate (44 mg) and sodium chlorite (73 mg)
  7. stirringthe mixture is stirred at room temperature for 30 minutes
  8. additionThereto are added ethyl acetate
  9. customa 1N-hydrochloric acid, and the mixture is separated
  10. washthe organic layer is washed with a saturated brine
  11. dry with materialdried over magnesium sulfate
  12. concentrationconcentrated under reduced pressure
  13. customThe resulting residue is purified by silica gel column chromatography (hexane:ethyl acetate=9:1→2:3)

Sources & evidence

ORD record
ord-46e7ab42791c4786a7e3a81640b93f73
Source dataset
uspto-grants-2011_03
Patent number
US07906517B2

Reaction notes

Loading…