Oxalyl chloride → Ethyl 5-(4-tert-butylbenzyl)-1,2,4-oxadiazole-3-carboxylate

HRID 58614Notes

Reaction equation

HRID 58614 reaction equation
[C:1]([C:5]1[CH:6]=[C:7](CC(O)=O)[CH:8]=[CH:9][CH:10]=1)([CH3:4])([CH3:3])[CH3:2].[C:15](Cl)(=O)[C:16](Cl)=O.[NH2:21][C:22](=[N:28][OH:29])[C:23]([O:25][CH2:26][CH3:27])=[O:24].C(N(CC)C(C)C)(C)C>ClCCl.O.CN(C=O)C>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([CH2:15][C:16]2[O:29][N:28]=[C:22]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[N:21]=2)=[CH:7][CH:6]=1)([CH3:2])([CH3:3])[CH3:4]

Participants

8

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 6785548Ethyl 2-amino-2-(hydroxyimino)acetateHCID 119590033-(1,1-Dimethylethyl)benzeneacetic acid

Product 1

HCID 66831957Ethyl 5-(4-tert-butylbenzyl)-1,2,4-oxadiazole-3-carboxylateYield 38.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

A mixture of 2-(3-tert-butylphenyl)acetic acid (0.728 g; 3.78 mmol) and oxalyl chloride (0.352 mL; 4.16 mmol) in dichloromethane (8 mL) with few drops of DMF was stirred at room temperature for 3 hours and added to a mixture of ethyl 2-amino-2-(hydroxyimino)acetate (0.500 g; 3.78 mmol) and N,N diisopropylethylamine (1.05 mL; 6.06 mmol) in dichloromethane (10 mL) at −15° C. The reaction mixture was stirred at room temperature for 60 h and poured into a mixture of ice and water. The organic layer was separated, dried over MgSO4 and concentrated under reduced pressure. The residue was refluxed in a sealed tube with pyridine (18 mL) for 20 h and concentrated under reduced pressure. The crude material was purified by flash chromatography on silica (eluent 20 to 100% ethyl acetate in heptane) to yield 0.422 g (30%) of the title compound as a yellow solid.

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 60 h
  2. customThe organic layer was separated
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated under reduced pressure
  5. temperatureThe residue was refluxed in a sealed tube with pyridine (18 mL) for 20 h
  6. concentrationconcentrated under reduced pressure
  7. customThe crude material was purified by flash chromatography on silica (eluent 20 to 100% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-07096ec0f557466d9da304383d6df2e6
Source dataset
uspto-grants-2016_09
Patent number
US09434722B2

Reaction notes

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