Acetic Acid → 1-[(4-{5-[4-Phenyl-5-(trifluoromethyl)-2-thienyl]-1,2,4-oxadiazol-3-yl}-2-furyl)methyl]azetidine-3-carboxylic acid

HRID 2247638Notes

Reaction equation

HRID 2247638 reaction equation
[C:1]1([C:7]2[CH:8]=[C:9]([C:16]3[O:20][N:19]=[C:18]([C:21]4[CH:22]=[C:23]([CH2:26][N:27]5[CH2:30][CH:29]([C:31]([O:33]CC)=[O:32])[CH2:28]5)[O:24][CH:25]=4)[N:17]=3)[S:10][C:11]=2[C:12]([F:15])([F:14])[F:13])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.O.[OH-].[Li+].C(O)(=O)C.C(O)(=O)C(O)=O>CO.O.O1CCCC1>[C:1]1([C:7]2[CH:8]=[C:9]([C:16]3[O:20][N:19]=[C:18]([C:21]4[CH:22]=[C:23]([CH2:26][N:27]5[CH2:30][CH:29]([C:31]([OH:33])=[O:32])[CH2:28]5)[O:24][CH:25]=4)[N:17]=3)[S:10][C:11]=2[C:12]([F:14])([F:13])[F:15])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 971Oxalic AcidHCID 168937Lithium hydroxide, monohydrateHCID 68528577HCID 68528577, compound

Product 1

HCID 119777061-[(4-{5-[4-Phenyl-5-(trifluoromethyl)-2-thienyl]-1,2,4-oxadiazol-3-yl}-2-furyl)methyl]azetidine-3-carboxylic acidYield 43.1%

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent2×HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of ethyl 1-[(4-{5-[4-phenyl-5-(trifluoromethyl)-2-thienyl]-1,2,4-oxadiazol-3-yl}-2-furyl)methyl]azetidine-3-carboxylate (0.20 g, 0.40 mmol) that was obtained in Example 1 (1f) in a mixed solvent of tetrahydrofuran (0.50 ml), methanol (0.50 ml) and water (0.50 ml) was added lithium hydroxide monohydrate (37 mg, 0.88 mmol) with stirring, and the resulting mixture was stirred at room temperature for 1 hour. After stirring, acetic acid (48 μl, 0.88 mmol) was added to the reaction mixture to quench the reaction. Subsequently, to the resulting mixture was added a solution of oxalic acid (18 mg, 0.20 mmol) in methanol (0.5 ml) with stirring, and the resulting mixture was stirred for 30 minutes. The white solid precipitated was collected by filtration using a Kiriyama funnel, washed with a mixed solvent of water and methanol (3:7), and dried in vacuo to afford the title compound (82 mg) in a yield of 39% as a white crystalline solid.

Workup

  1. stirringthe resulting mixture was stirred at room temperature for 1 hour
  2. stirringAfter stirring
  3. customto quench
  4. customthe reaction
  5. stirringwith stirring
  6. stirringthe resulting mixture was stirred for 30 minutes
  7. customThe white solid precipitated
  8. filtrationwas collected by filtration
  9. washwashed with a mixed solvent of water and methanol (3:7)
  10. customdried in vacuo

Sources & evidence

ORD record
ord-21928229e08649829e1c79204a0db8b5
Source dataset
uspto-grants-2010_03
Patent number
US07687491B2

Reaction notes

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