Triethylamine → 3-{1-{2-{[2-(4-Tert-butylthiazol-2-yl)benzofuran-5-yloxy]methyl}phenoxy}butyl}-1,2,4-oxadiazoline-5-one

HRID 1604701Notes

Reaction equation

HRID 1604701 reaction equation
[C:1]([C:5]1[N:6]=[C:7]([C:10]2[O:11][C:12]3[CH:18]=[CH:17][C:16]([O:19][CH2:20][C:21]4[CH:35]=[CH:34][CH:33]=[CH:32][C:22]=4[O:23][CH:24]([CH2:29][CH2:30][CH3:31])[C:25](=[N:27][OH:28])[NH2:26])=[CH:15][C:13]=3[CH:14]=2)[S:8][CH:9]=1)([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.Cl[C:44](OCC)=[O:45]>O1CCCC1>[C:1]([C:5]1[N:6]=[C:7]([C:10]2[O:11][C:12]3[CH:18]=[CH:17][C:16]([O:19][CH2:20][C:21]4[CH:35]=[CH:34][CH:33]=[CH:32][C:22]=4[O:23][CH:24]([C:25]4[NH:26][C:44](=[O:45])[O:28][N:27]=4)[CH2:29][CH2:30][CH3:31])=[CH:15][C:13]=3[CH:14]=2)[S:8][CH:9]=1)([CH3:2])([CH3:3])[CH3:4]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 867548822-{2-{[2-(4-Tert-butylthiazol-2-yl)benzofuran-5-yloxy]methyl}phenoxy}pentanamide oxime

Product 1

HCID 1360908323-{1-{2-{[2-(4-Tert-butylthiazol-2-yl)benzofuran-5-yloxy]methyl}phenoxy}butyl}-1,2,4-oxadiazoline-5-oneYield 47.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

2-{2-{[2-(4-tert-Butylthiazol-2-yl)benzofuran-5-yloxy]methyl}phenoxy}pentanamide oxime (240 mg) and triethylamine (61 mg) were dissolved in tetrahydrofuran (3 ml). To this solution was added a solution of ethyl chloroformate (65 mg) dissolved in tetrahydrofuran (1 ml) under ice-cooling. The reaction mixture was stirred for fifteen minutes, filtered, and concentrated. The resulting material was dissolved in xylene (4 ml) and 1.8-diazabicyclo[5.4.0]undec-7-ene (152 mg) was added. The mixture was stirred at 50° C. for three hours. The mixture was cooled, diluted with toluene, and washed successively with 0.5N hydrochloric acid and brine, and dried over magnesium sulfate. The crude material was purified on a silica gel column eluting with a mixed solvent of methylene chloride and methanol (1% vol.) to give partially purified product which was again purified on a silica gel column eluting with a mixed solvent of toluene and ethyl acetate (6:1) to give 3-{1-{2-{[2-(4-tert-butylthiazol-2-yl)benzofuran-5-yloxy]methyl}phenoxy}butyl}-1,2,4-oxadiazoline-5-one (120 mg).

Workup

  1. temperaturecooling
  2. filtrationfiltered
  3. concentrationconcentrated
  4. dissolutionThe resulting material was dissolved in xylene (4 ml)
  5. addition1.8-diazabicyclo[5.4.0]undec-7-ene (152 mg) was added
  6. stirringThe mixture was stirred at 50° C. for three hours
  7. temperatureThe mixture was cooled
  8. additiondiluted with toluene
  9. washwashed successively with 0.5N hydrochloric acid and brine
  10. dry with materialdried over magnesium sulfate
  11. customThe crude material was purified on a silica gel column
  12. washeluting with a mixed solvent of methylene chloride and methanol (1% vol.)
  13. customto give partially purified product which
  14. customwas again purified on a silica gel column
  15. washeluting with a mixed solvent of toluene and ethyl acetate (6:1)

Sources & evidence

ORD record
ord-2f858125864646d389329326a88a7e13
Source dataset
uspto-grants-1999_11
Patent number
US05994378

Reaction notes

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