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

HRID 732228Notes

Reaction equation

HRID 732228 reaction equation
[C:1]1([C:7]2[N:8]=[C:9]([CH:12]=O)[S:10][CH:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH2:14][C:15]1[CH:34]=[CH:33][C:18]([CH2:19][O:20][C:21]2[CH:26]=[CH:25][C:24]([CH2:27][CH2:28][C:29]([O:31]C)=[O:30])=[CH:23][CH:22]=2)=[CH:17][CH:16]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[C:49]1([CH2:55][CH:56]=O)[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1.[OH-].[Na+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>O.O1CCCC1.C(O)C.ClCCCl.C(O)(=O)C>[C:49]1([CH2:55][CH2:56][N:14]([CH2:12][C:9]2[S:10][CH:11]=[C:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[N:8]=2)[C:15]2[CH:34]=[CH:33][C:18]([CH2:19][O:20][C:21]3[CH:26]=[CH:25][C:24]([CH2:27][CH2:28][C:29]([OH:31])=[O:30])=[CH:23][CH:22]=3)=[CH:17][CH:16]=2)[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1

Participants

12

Reactant 6

HCID 311Citric AcidHCID 998PhenylacetaldehydeHCID 14798Sodium HydroxideHCID 35388144-Phenyl-1,3-thiazole-2-carbaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 23143251Methyl 3-(4-((4-aminobenzyl)oxy)phenyl)propanoate

Product 1

HCID 231432483-{4-[(4-{(2-Phenylethyl)[(4-phenyl-1,3-thiazol-2-yl)methyl]amino}benzyl)oxy]phenyl}propanoic acidYield 24.3%

Reagents, catalysts & solvents 5

HCID 111,2-DichloroethaneSolventHCID 176Acetic AcidSolventHCID 702EthanolSolventHCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of 4-phenyl-1,3-thiazole-2-carbaldehyde (380 mg, 2.0 mmol), methyl 3-{4-[(4-aminobenzyl)oxy]phenyl}-propanoate (570 mg, 2.0 mmol), acetic acid (0.1 mL) and 1,2-dichloroethane (5 mL) was added sodium triacetoxyborohydride (1.2 g, 5.7 mmol) under ice-cooling. The mixture was allowed to warm to room temperature and stirred for 1 hr. Phenylacetoaldehyde (35-50% diethyl phthalate solution, 480 mg) was added to the reaction mixture, and the mixture was further stirred at room temperature for 1 hr. The reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:19-1:2 in volume ratio) to give a yellow oil. To a mixture of the oil, ethanol (5 mL) and tetrahydrofuran (5 mL) was added 2N aqueous sodium hydroxide solution (2 mL), and the mixture was stirred at room temperature for 14 hr. The reaction mixture was diluted with water, neutralized with 10% aqueous citric acid solution, and extracted with ethyl acetate. The organic layer was concentrated and the residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:4-4:1 in volume ratio) to give the title compound (267 mg, yield 24%) as a yellow oil.

Workup

  1. temperaturecooling
  2. stirringthe mixture was further stirred at room temperature for 1 hr
  3. extractionextracted with ethyl acetate
  4. washThe organic layer was washed with saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:19-1:2 in volume ratio)
  8. customto give a yellow oil
  9. stirringthe mixture was stirred at room temperature for 14 hr
  10. extractionextracted with ethyl acetate
  11. concentrationThe organic layer was concentrated
  12. customthe residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:4-4:1 in volume ratio)

Sources & evidence

ORD record
ord-652205f344fb41a9ba44cbf986e91ebb
Source dataset
uspto-grants-2009_09
Patent number
US07585880B2

Reaction notes

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