Hydrochloric Acid → Ethyl 3-[2-fluoro-4-({4-[(propyl{4-[4-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl}amino)methyl]benzyl}oxy)phenyl]propanoate

HRID 732188Notes

Reaction equation

HRID 732188 reaction equation
[CH2:1]([NH:4][C:5]1[S:6][CH:7]=[C:8]([C:10]2[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][CH:11]=2)[N:9]=1)[CH2:2][CH3:3].[H-].[Na+].Cl[CH2:23][C:24]1[CH:45]=[CH:44][C:27]([CH2:28][O:29][C:30]2[CH:35]=[CH:34][C:33]([CH2:36][CH2:37][C:38]([O:40][CH2:41][CH3:42])=[O:39])=[C:32]([F:43])[CH:31]=2)=[CH:26][CH:25]=1.Cl>CN(C)C=O>[F:43][C:32]1[CH:31]=[C:30]([O:29][CH2:28][C:27]2[CH:44]=[CH:45][C:24]([CH2:23][N:4]([CH2:1][CH2:2][CH3:3])[C:5]3[S:6][CH:7]=[C:8]([C:10]4[CH:11]=[CH:12][C:13]([C:16]([F:19])([F:17])[F:18])=[CH:14][CH:15]=4)[N:9]=3)=[CH:25][CH:26]=2)[CH:35]=[CH:34][C:33]=1[CH2:36][CH2:37][C:38]([O:40][CH2:41][CH3:42])=[O:39]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 23082955N-Propyl-4-[4-(trifluoromethyl)phenyl]-1,3-thiazol-2-amineHCID 23143241Ethyl 3-(4-([4-(chloromethyl)benzyl]oxy}-2-fluorophenyl)propanoate

Product 1

HCID 23143337Ethyl 3-[2-fluoro-4-({4-[(propyl{4-[4-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl}amino)methyl]benzyl}oxy)phenyl]propanoate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of N-propyl-4-[4-(trifluoromethyl)phenyl]-1,3-thiazole-2-amine (700 mg, 2.44 mmol) in N,N-dimethylformamide (5 mL) was added sodium hydride (100 mg, in oil, 2.5 mmol) at room temperature and the mixture was stirred at room temperature for 1 hr. Ethyl 3-(4-{[4-(chloromethyl)benzyl]oxy}-2-fluorophenyl)propanoate (700 mg, 2.0 mmol) was added and the mixture was further stirred at room temperature for 2 hr. The reaction mixture was poured into 1N hydrochloric acid and the mixture was extracted with ethyl acetate. The organic layer was concentrated and the residue was purified by preparative HPLC. The obtained fraction was concentrated, neutralized with 10% aqueous sodium hydrogencarbonate solution, and extracted with ethyl acetate. The ethyl acetate layer was filtered with a Presep Dehydration tube (Wako Pure Chemical Industries, Ltd.) and concentrated to give the title compound as a yellow oil.

Workup

  1. stirringthe mixture was further stirred at room temperature for 2 hr
  2. extractionthe mixture was extracted with ethyl acetate
  3. concentrationThe organic layer was concentrated
  4. customthe residue was purified by preparative HPLC
  5. concentrationThe obtained fraction was concentrated
  6. extractionextracted with ethyl acetate
  7. filtrationThe ethyl acetate layer was filtered with a Presep Dehydration tube (Wako Pure Chemical Industries, Ltd.)
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-393ba54bbc1a4255b272aa1a8fa4dddd
Source dataset
uspto-grants-2009_09
Patent number
US07585880B2

Reaction notes

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