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

HRID 1008298Notes

Reaction equation

HRID 1008298 reaction equation
C[O:2][C:3](=[O:45])[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(C(=O)CO)=CC=2CC)[C:12]=1[CH2:42][CH2:43][CH3:44].S(OS(C(F)(F)F)(=O)=O)(C(F)(F)F)(=O)=O.[N:61]1[C:66]([CH3:67])=[CH:65][CH:64]=[CH:63][C:62]=1[CH3:68].C[CH2:70][O:71]CC>C(Cl)Cl.O>[CH2:62]([C:63]1[CH:64]=[C:65]([C:66]2[N:61]=[CH:70][O:71][CH:67]=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]([CH2:42][CH2:43][CH3:44])=[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:45])=[O:2])[CH3:68]

Participants

7

Reactant 4

HCID 3283Diethyl EtherHCID 79372,6-LutidineHCID 67749Trifluoromethanesulfonic anhydrideHCID 601111952-(3-{3-[5-Benzyloxy-2-ethyl-4-(2-hydroxyacetyl)phenoxy]propoxy)-2-propylphenoxy)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 6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 2-(3-{3-[5-benzyloxy-2-ethyl-4-(2-hydroxyacetyl)phenoxy]propoxy}-2-propylphenoxy)benzoic acid methyl ester (1.39 g, 2.27 mmol) in methylene chloride (20 mL) cooled to −78° C. was added triflic anhydride (0.57 mL, 3.4 mmol) and 2,6-lutidine (0.40 mL, 3.4 mmol). The resulting mixture was stirred for 1 h then poured into ether and water. The organic layer was separated and washed once with saturated sodium chloride solution, dried (sodium sulfate), filtered, and concentrated in vacuo. The residue was dissolved in a 2:1 mixture of formamide/N,N-dimethylformamide (9 mL) and heated at 120° C. in a sealed tube for 4 h. The mixture was cooled to room temperature and diluted with ethyl acetate. The mixture was washed four times with water, once with saturated sodium chloride solution, dried (sodium sulfate), filtered, and concentrated in vacuo. Chromatography (silica gel, 10% ethyl acetate/90% hexane) of the residue provided 89 mg (6%) of the title product as a colorless oil. 1H NMR (CDCl3) δ 7.92 (s, 1H), 7.85 (s, 1H), 7.83 (m, 2H), 7.35 (m, 6H), 7.03 (d, J=8 Hz, 1H), 7.00 (d, J=8 Hz, 1H), 6.73 (d, J=8 Hz, 1H), 6.62 (d, J=8 Hz, 1H), 6.52 (s, 1H), 6.35 (d, J=8 Hz, 1H), 5.07 (s, 2H), 4.14 (m, 4H), 3.76 (s, 3H), 2.61 (m, 4H), 2.26 (quintet, J=6 Hz, 2H), 1.48 (hextet, J=7 Hz, 2H), 1.15 (t, J=8 Hz, 3H), 0.84 (t, J=8 Hz, 3H).

Workup

  1. customThe organic layer was separated
  2. washwashed once with saturated sodium chloride solution
  3. dry with materialdried (sodium sulfate)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. dissolutionThe residue was dissolved in a 2:1 mixture of formamide/N,N-dimethylformamide (9 mL)
  7. temperatureThe mixture was cooled to room temperature
  8. additiondiluted with ethyl acetate
  9. washThe mixture was washed four times with water
  10. dry with materialonce with saturated sodium chloride solution, dried (sodium sulfate)
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-cee1db98e6f24b41b2dec99ad68a7553
Source dataset
uspto-grants-2004_09
Patent number
US06797723B1

Reaction notes

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