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

HRID 2422283Notes

Reaction equation

HRID 2422283 reaction equation
Br.[CH2:2]([NH:5][C:6]1[S:7][CH:8]=[C:9]([C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][CH:12]=2)[N:10]=1)[CH2:3][CH3:4].[H-].[Na+].Cl[CH2:24][C:25]1[CH:44]=[CH:43][C:28]([CH2:29][O:30][C:31]2[CH:36]=[CH:35][C:34]([CH2:37][CH2:38][C:39]([O:41]C)=[O:40])=[CH:33][CH:32]=2)=[CH:27][CH:26]=1.[OH-].[Na+].Cl>CN(C)C=O.CO.O>[CH2:2]([N:5]([CH2:24][C:25]1[CH:44]=[CH:43][C:28]([CH2:29][O:30][C:31]2[CH:36]=[CH:35][C:34]([CH2:37][CH2:38][C:39]([OH:41])=[O:40])=[CH:33][CH:32]=2)=[CH:27][CH:26]=1)[C:6]1[S:7][CH:8]=[C:9]([C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:19])([F:20])[F:18])=[CH:13][CH:12]=2)[N:10]=1)[CH2:3][CH3:4]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 23082857Methyl 3-(4-([4-(chloromethyl)benzyl]oxy)phenyl)propanoateHCID 23082954N-propyl-4-[4-(trifluoromethyl)phenyl]-1,3-thiazol-2-amine hydrobromide

Product 1

HCID 575419773-[4-({4-[(Propyl{4-[4-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl}amino)methyl]benzyl}oxy)phenyl]propanoic acidYield 42%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of N-propyl-4-[4-(trifluoromethyl)phenyl]-1,3-thiazol-2-amine hydrobromide (477 mg) in N,N-dimethylformamide (10 mL) was added sodium hydride (60%, oil, 104 mg) at 0° C., the temperature was raised to room temperature and the mixture was stirred for 30 min. Methyl 3-(4-{[4-(chloromethyl)benzyl]oxy}phenyl)propanoate (318 mg) was added to the reaction mixture at 0° C., the temperature was raised to room temperature and the mixture was stirred for 1 hr. The reaction mixture was poured into water, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was concentrated, and the residue was purified by silica gel column chromatography with ethyl acetate-hexane (gradient of 1:19 to 1:1 by volume ratio) to give a pale-yellow oil. This oil was dissolved in methanol (5 mL), 2N aqueous sodium hydroxide solution (5 mL) was added, and the mixture was stirred at room temperature for 3 hr. The reaction mixture was poured into 1N aqueous hydrochloric acid solution, and the precipitated solid was collected by filtration, washed successively with water and isopropyl ether and dried to give the title compound (230 mg, yield 42%) as colorless crystals.

Workup

  1. temperaturethe temperature was raised to room temperature
  2. stirringthe mixture was stirred for 1 hr
  3. extractionthe mixture was extracted with ethyl acetate
  4. concentrationThe ethyl acetate layer was concentrated
  5. customthe residue was purified by silica gel column chromatography with ethyl acetate-hexane (gradient of 1:19 to 1:1 by volume ratio)
  6. customto give a pale-yellow oil
  7. stirringthe mixture was stirred at room temperature for 3 hr
  8. filtrationthe precipitated solid was collected by filtration
  9. washwashed successively with water and isopropyl ether
  10. customdried

Sources & evidence

ORD record
ord-c32bae68677b4b78845a096ed2bedda5
Source dataset
uspto-grants-2011_06
Patent number
US07960369B2

Reaction notes

Loading…