Oxalyl chloride → HCID 58541902, compound

HRID 1966722Notes

Reaction equation

HRID 1966722 reaction equation
[CH3:1][O:2][C:3](=[O:15])[C:4]1[C:5](=[CH:9][CH:10]=[C:11]([O:13][CH3:14])[CH:12]=1)[C:6]([OH:8])=O.C(Cl)(=O)C(Cl)=O.COC(=O)C1C=C(Cl)C=CC=1C(Cl)=O.O[NH:37][C:38](=[NH:40])[CH3:39]>C(Cl)Cl.CN(C=O)C.N1C=CC=CC=1.CCOC(C)=O>[CH3:1][O:2][C:3](=[O:15])[C:4]1[CH:12]=[C:11]([O:13][CH3:14])[CH:10]=[CH:9][C:5]=1[C:6]1[O:8][N:40]=[C:38]([CH3:39])[N:37]=1

Participants

9

Reactant 4

HCID 65578Oxalyl chlorideHCID 58542053HCID 58542053, compoundHCID 86660010HCID 86660010, compoundHCID 178465666HCID 178465666, compound

Product 1

HCID 58541902HCID 58541902, compoundYield 60%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 1049PyridineSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of crude 4-methoxy-phthalic acid 2-methyl ester (850 mg) in CH2Cl2 (25 mL) is added oxalyl chloride (3.0 mL) and DMF (1 drop). The reaction mixture is stirred at room temperature for 1 hour, and is concentrated under reduced pressure. To the freshly formed 5-chloro-2-chlorocarbonyl-benzoic acid methyl ester in pyridine (5.0 mL) is added N-hydroxy-acetamidine (350 mg, 4.72 mmol). The reaction mixture is heated at 100° C. for 16 hours. The reaction mixture is allowed to cool to room temperature, diluted with EtOAc (100 mL), and washed with H2O (75 mL×2). The organic layer is dried with Na2SO4 and is filtered. The filtrate is concentrated under reduced pressure and the residue is purified by silica gel flash column chromatography with 35% EtOAc in heptanes as the eluent to afford 5-methoxy-2-(3-methyl-1,2,4-oxadiazol-5-yl)-benzoic acid methyl ester (600 mg, 60%).

Workup

  1. concentrationis concentrated under reduced pressure
  2. temperatureThe reaction mixture is heated at 100° C. for 16 hours
  3. temperatureto cool to room temperature
  4. washwashed with H2O (75 mL×2)
  5. dry with materialThe organic layer is dried with Na2SO4
  6. filtrationis filtered
  7. concentrationThe filtrate is concentrated under reduced pressure
  8. customthe residue is purified by silica gel flash column chromatography with 35% EtOAc in heptanes as the eluent

Sources & evidence

ORD record
ord-968ab2b458db4461ac734f7a517b70e0
Source dataset
uspto-grants-2013_04
Patent number
US08420655B2

Reaction notes

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