Water → 2-{3-[3-(2-Ethyl-5-hydroxy-4-oxazol-4-yl-phenoxy)propoxy]-2-propyl-phenoxy}benzoic acid

HRID 1008297Notes

Reaction equation

HRID 1008297 reaction equation
C[O:2][C:3](=[O:44])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[O:10][C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([O:17][CH2:18][CH2:19][CH2:20][O:21][C:22]2[CH:27]=[C:26]([O:28]CC3C=CC=CC=3)[C:25](C(=O)C)=[CH:24][C:23]=2[CH2:39]C)[C:12]=1[CH2:41][CH2:42][CH3:43].O.FC(F)(F)[C:48]([OH:50])=O.F[C:54](F)(F)C(OI(C1C=CC=CC=1)OC(=O)C(F)(F)F)=O.[C:74](#[N:76])[CH3:75]>>[CH2:24]([C:23]1[CH:39]=[C:75]([C:74]2[N:76]=[CH:54][O:50][CH:48]=2)[C:26]([OH:28])=[CH:27][C:22]=1[O:21][CH2:20][CH2:19][CH2:18][O:17][C:13]1[C:12]([CH2:41][CH2:42][CH3:43])=[C:11]([CH:16]=[CH:15][CH:14]=1)[O:10][C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=1[C:3]([OH:2])=[O:44])[CH3:25]

Participants

6

Reactant 5

HCID 962WaterHCID 6342AcetonitrileHCID 6422Trifluoroacetic acidHCID 102317Bis(trifluoroacetoxy)iodobenzeneHCID 601111702-{3-[3-(4-Acetyl-5-benzyloxy-2-ethylphenoxy)propoxy]-2-propyl-phenoxy}benzoic acid methyl ester

Product 1

HCID 98066212-{3-[3-(2-Ethyl-5-hydroxy-4-oxazol-4-yl-phenoxy)propoxy]-2-propyl-phenoxy}benzoic acidYield 31%

Procedure

A mixture of 2-{3-[3-(4-acetyl-5-benzyloxy-2-ethylphenoxy)propoxy]-2-propyl-phenoxy}benzoic acid methyl ester (5.31 g, 8.89 mmol) and water (10 mL) in acetonitrile (50 mL) was treated with trifluoroacetic acid (1.4 mL), 18 mmol) and [bis(trifluoroacetoxy)iodo]benzene (7.65 g, 17.8 mmol). The resulting mixture was heated at reflux for 4 h then concentrated in vacuo. The residue was dissolved in methylene chloride and washed once with water. The aqueous layer was extracted twice with fresh portions of methylene chloride. The combined organic layers were washed three times with saturated sodium bicarbonate solution, once with saturated sodium chloride solution, dried (sodium sulfate), filtered, and concentrated in vacuo. Chromatography (silica gel, 20% ethyl acetate/80% hexane) of the residue provided 1.68 g (31%) of the title compound as a brown oil. 1H NMR (CDCl3) δ 7.92 (s, 1H), 7.88 (d, J=9 Hz, 1H), 7.40 (m, 6H), 7.12 (d, J=9 Hz, 1H), 7.05 (d, J=9 Hz, 1H), 6.79 (d, J=8 Hz, 1H), 6.66 (d, J=8 Hz, 1H), 6.50 (s, 1H), 6.43 (d, J=8 Hz, 1H), 5.15 (s, 2H), 4.65 (s, 2H), 4.22 (m. 4H), 3.83 (s, 3H), 2.65 (m, 4H), 2.34 (quintet, J=6 Hz, 2H), 1.55 (hextet, J=7 Hz, 2H), 1.17 (t, J=8 Hz, 3H), 0.89 (t, J=8 Hz, 3H); TOS MS ES+ exact mass calculated for C37H41O8 (p+1): m/z=613.2801. Found: 613.2833.

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureat reflux for 4 h
  3. concentrationthen concentrated in vacuo
  4. dissolutionThe residue was dissolved in methylene chloride
  5. washwashed once with water
  6. extractionThe aqueous layer was extracted twice with fresh portions of methylene chloride
  7. washThe combined organic layers were washed three times with saturated sodium bicarbonate solution
  8. dry with materialonce with saturated sodium chloride solution, dried (sodium sulfate)
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-b96213f78ecb4ce9b6200615d66bb4d8
Source dataset
uspto-grants-2004_09
Patent number
US06797723B1

Reaction notes

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