Hydrochloric Acid → 3-(2-Fluoro-4-[(4-{[[2-(2-fluorophenyl)ethyl](4-isopropyl-1,3-thiazol-2-yl)amino]methyl}benzyl)oxy]phenyl}-propanoic acid

HRID 732215Notes

Reaction equation

HRID 732215 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][CH2:9][NH:10][C:11]1[S:12][CH:13]=[C:14]([CH:16]([CH3:18])[CH3:17])[N:15]=1.[H-].[Na+].Cl[CH2:22][C:23]1[CH:44]=[CH:43][C:26]([CH2:27][O:28][C:29]2[CH:34]=[CH:33][C:32]([CH2:35][CH2:36][C:37]([O:39]CC)=[O:38])=[C:31]([F:42])[CH:30]=2)=[CH:25][CH:24]=1.[OH-].[Na+].Cl>CN(C)C=O.C(O)C.O>[F:42][C:31]1[CH:30]=[C:29]([O:28][CH2:27][C:26]2[CH:43]=[CH:44][C:23]([CH2:22][N:10]([CH2:9][CH2:8][C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=3[F:1])[C:11]3[S:12][CH:13]=[C:14]([CH:16]([CH3:18])[CH3:17])[N:15]=3)=[CH:24][CH:25]=2)[CH:34]=[CH:33][C:32]=1[CH2:35][CH2:36][C:37]([OH:39])=[O:38]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 23143241Ethyl 3-(4-([4-(chloromethyl)benzyl]oxy}-2-fluorophenyl)propanoateHCID 23143247N-[2-(2-fluorophenyl)ethyl]-4-isopropyl-1,3-thiazole-2-amine

Product 1

HCID 231432733-(2-Fluoro-4-[(4-{[[2-(2-fluorophenyl)ethyl](4-isopropyl-1,3-thiazol-2-yl)amino]methyl}benzyl)oxy]phenyl}-propanoic acidYield 75%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent

Procedure

To a solution of N-[2-(2-fluorophenyl)ethyl]-4-isopropyl-1,3-thiazole-2-amine (139 mg) in N,N-dimethylformamide (2 mL) was added sodium hydride (20 mg), and the mixture was stirred at room temperature for 1 hr. Ethyl 3-(4-{[4-(chloromethyl)benzyl]oxy}-2-fluorophenyl)propanoate (175 mg) was added to the reaction mixture at room temperature, and the mixture was stirred at room temperature for 1 hr. The reaction mixture was poured into water and extracted with ethyl acetate. The ethyl acetate layer was dried using a Presep Dehydration tube (manufactured by Wako Pure Chemical Industries, Ltd.), and 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. This oil was dissolved in ethanol (5 mL), 2N aqueous sodium hydroxide solution (2 mL) was added, and the mixture was stirred at room temperature for 1 hr. The reaction mixture was diluted with water, neutralized with 1N hydrochloric acid, and extracted with ethyl acetate. The extract was dried using a Presep Dehydration tube (manufactured by Wako Pure Chemical Industries, Ltd.) and concentrated to give the title compound (206 mg, yield 71%) as a yellow oil.

Workup

  1. stirringthe mixture was stirred at room temperature for 1 hr
  2. extractionextracted with ethyl acetate
  3. dry with materialThe ethyl acetate layer was dried
  4. concentrationconcentrated
  5. customThe residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:19-1:1 in volume ratio)
  6. customto give a yellow oil
  7. stirringthe mixture was stirred at room temperature for 1 hr
  8. extractionextracted with ethyl acetate
  9. customThe extract was dried
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-8ab355549dea465589b9cfc823924939
Source dataset
uspto-grants-2009_09
Patent number
US07585880B2

Reaction notes

Loading…