Sodium hydride → 3-[4-({4-[([2-(4-Fluorophenyl)ethyl]{4-[4-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl}amino)methyl]-benzyl}oxy)phenyl]propanoic acid

HRID 732226Notes

Reaction equation

HRID 732226 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][NH:10][C:11]2[S:12][CH:13]=[C:14]([C:16]3[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][CH:17]=3)[N:15]=2)=[CH:4][CH:3]=1.[H-].[Na+].Cl[CH2:29][C:30]1[CH:49]=[CH:48][C:33]([CH2:34][O:35][C:36]2[CH:41]=[CH:40][C:39]([CH2:42][CH2:43][C:44]([O:46]C)=[O:45])=[CH:38][CH:37]=2)=[CH:32][CH:31]=1>CN(C)C=O.C(O)C.O1CCCC1.[OH-].[Na+].O.Cl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][N:10]([CH2:29][C:30]2[CH:49]=[CH:48][C:33]([CH2:34][O:35][C:36]3[CH:41]=[CH:40][C:39]([CH2:42][CH2:43][C:44]([OH:46])=[O:45])=[CH:38][CH:37]=3)=[CH:32][CH:31]=2)[C:11]2[S:12][CH:13]=[C:14]([C:16]3[CH:21]=[CH:20][C:19]([C:22]([F:23])([F:25])[F:24])=[CH:18][CH:17]=3)[N:15]=2)=[CH:4][CH:3]=1

Participants

10

Reactant 3

HCID 24758Sodium hydrideHCID 23082857Methyl 3-(4-([4-(chloromethyl)benzyl]oxy)phenyl)propanoateHCID 23143240N-[2-(4-fluorophenyl)ethyl]-4-[4-(trifluoromethyl)phenyl]-1,3-thiazole-2-amine

Product 1

HCID 231432723-[4-({4-[([2-(4-Fluorophenyl)ethyl]{4-[4-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl}amino)methyl]-benzyl}oxy)phenyl]propanoic acidYield 17.2%

Reagents, catalysts & solvents 6

HCID 313Hydrochloric AcidSolvent2×HCID 702EthanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 14798Sodium HydroxideSolvent

Procedure

To a solution of N-[2-(4-fluorophenyl)ethyl]-4-[4-(trifluoromethyl)phenyl]-1,3-thiazole-2-amine (400 mg, 1.09 mmol) in N,N-dimethylformamide (5 mL) was added sodium hydride (50 mg, in oil, 1.3 mmol) at room temperature, and the mixture was stirred at room temperature for 1 hr. Methyl 3-(4-{[4-(chloromethyl)benzyl]oxy}phenyl)propanoate (318 mg, 1.0 mmol) was added, and the mixture was further stirred at room temperature for 1 hr. The reaction mixture was poured into 1N hydrochloric acid and extracted with ethyl acetate. The organic layer was concentrated. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:19-1:1 in volume ratio) to give a yellow oil. The oil was dissolved in a mixed solvent of ethanol (5 mL) and tetrahydrofuran (5 mL), and 2N aqueous sodium hydroxide solution (2 mL) was added. The mixture was stirred at room temperature for 2 hr. The reaction mixture was diluted with water and neutralized with 1N hydrochloric acid. The precipitated solid was collected by filtration, washed with water and dried to give the title compound (109 mg, yield 17%, 2 steps) as colorless crystals.

Workup

  1. stirringthe mixture was further stirred at room temperature for 1 hr
  2. extractionextracted with ethyl acetate
  3. concentrationThe organic layer was concentrated
  4. customThe residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:19-1:1 in volume ratio)
  5. customto give a yellow oil
  6. additionwas added
  7. stirringThe mixture was stirred at room temperature for 2 hr
  8. filtrationThe precipitated solid was collected by filtration
  9. washwashed with water
  10. customdried

Sources & evidence

ORD record
ord-148b268ead55486dbdfa1262b29f1b63
Source dataset
uspto-grants-2009_09
Patent number
US07585880B2

Reaction notes

Loading…