Tetrahydrofuran → (4-Ethyl-5-{5-[4-(2-fluorophenoxy)phenyl]-1,2,4-oxadiazol-3-yl}-2-thienyl)methanol

HRID 2247688Notes

Reaction equation

HRID 2247688 reaction equation
[Si]([O:8][CH2:9][C:10]1[S:14][C:13]([C:15](=[N:17][OH:18])[NH2:16])=[C:12]([CH2:19][CH3:20])[CH:11]=1)(C(C)(C)C)(C)C.[F:21][C:22]1[CH:37]=[CH:36][CH:35]=[CH:34][C:23]=1[O:24][C:25]1[CH:33]=[CH:32][C:28]([C:29](O)=O)=[CH:27][CH:26]=1.C1(N=C=NC2CCCCC2)CCCCC1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.O1CCCC1>ClCCl.O.CCCCCC>[CH2:19]([C:12]1[CH:11]=[C:10]([CH2:9][OH:8])[S:14][C:13]=1[C:15]1[N:16]=[C:29]([C:28]2[CH:32]=[CH:33][C:25]([O:24][C:23]3[CH:34]=[CH:35][CH:36]=[CH:37][C:22]=3[F:21])=[CH:26][CH:27]=2)[O:18][N:17]=1)[CH3:20]

Participants

9

Reactant 5

HCID 8028TetrahydrofuranHCID 10868DicyclohexylcarbodiimideHCID 2724141Tetrabutylammonium FluorideHCID 200595614-(2-Fluorophenoxy)benzoic acidHCID 725011755-({[t-Butyl(dimethyl)silyl]oxy}methyl)-3-ethyl-N'-hydroxythiophene-2-carboximidamide

Product 1

HCID 68521923(4-Ethyl-5-{5-[4-(2-fluorophenoxy)phenyl]-1,2,4-oxadiazol-3-yl}-2-thienyl)methanolYield 89%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8058HexaneSolvent

Procedure

To a solution of 5-({[t-butyl(dimethyl)silyl]oxy}methyl)-3-ethyl-N′-hydroxythiophene-2-carboximidamide (0.16 g, 0.50 mmol) that was obtained in Example 10 (10d) and 4-(2-fluorophenoxy)benzoic acid (0.13 g, 0.55 mmol) that was obtained in Example 10 (10e) in dichloromethane (1.5 ml) was added N,N′-dicyclohexylcarbodiimide (0.11 g, 0.55 mmol) with stirring, and the resulting mixture was stirred at room temperature for 30 minutes. After stirring, hexane (2 ml) was added to the reaction mixture, and insoluble materials were removed by filtration, and the filtrate obtained was evaporated in vacuo. Subsequently, to a solution of the residue obtained in tetrahydrofuran (1 ml) was added a 1.0 M solution of tetrabutylammonium fluoride in tetrahydrofuran (0.75 ml, 0.75 mmol) with stirring, and the resulting mixture was stirred at 60° C. for 1 hour. After cooling to room temperature, the reaction mixture was poured into water (10 ml) and extracted with ether. The extract was washed with a saturated aqueous solution of sodium chloride and dried over magnesium sulfate. After filtration, the filtrate was evaporated in vacuo, and the crude product of the title compound thus obtained was purified by chromatography on a silica gel column using a mixed solvent of ethyl acetate and hexane (3:7 to 5:5) as the eluent to afford the title compound (0.18 g) in a yield of 89% as a white crystalline solid.

Workup

  1. stirringthe resulting mixture was stirred at room temperature for 30 minutes
  2. stirringAfter stirring
  3. customwere removed by filtration
  4. customthe filtrate obtained
  5. customwas evaporated in vacuo
  6. customSubsequently, to a solution of the residue obtained in tetrahydrofuran (1 ml)
  7. stirringwith stirring
  8. stirringthe resulting mixture was stirred at 60° C. for 1 hour
  9. extractionextracted with ether
  10. washThe extract was washed with a saturated aqueous solution of sodium chloride
  11. dry with materialdried over magnesium sulfate
  12. filtrationAfter filtration
  13. customthe filtrate was evaporated in vacuo

Sources & evidence

ORD record
ord-786e686eeafb41da88f18da9ab72bd9f
Source dataset
uspto-grants-2010_03
Patent number
US07687491B2

Reaction notes

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