Oxalyl chloride → HCID 66629416, compound

HRID 1429219Notes

Reaction equation

HRID 1429219 reaction equation
[Cl:1][C:2]1[C:10]([N+:11]([O-:13])=[O:12])=[CH:9][C:5]([C:6]([OH:8])=O)=[C:4]([F:14])[CH:3]=1.[C:15](Cl)(=O)C(Cl)=O.C[Mg+].[Br-]>C(Cl)Cl.CN(C=O)C.C1COCC1.[Zn+2].[Br-].[Br-].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:1][C:2]1[C:10]([N+:11]([O-:13])=[O:12])=[CH:9][C:5]([C:6](=[O:8])[CH3:15])=[C:4]([F:14])[CH:3]=1

Participants

9

Reactant 3

HCID 65578Oxalyl chlorideHCID 37745534-chloro-2-fluoro-5-nitrobenzoic acidHCID 178418689HCID 178418689, compound

Product 1

HCID 66629416HCID 66629416, compoundYield 74.3%

Reagents, catalysts & solvents 5

HCID 6228DimethylformamideCatalystHCID 10421208Zinc bromideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 4-chloro-2-fluoro-5-nitrobenzoic acid (16.0 g, 72.9 mmol) in anhydrous CH2Cl2 (400 mL) was added oxalyl chloride (9.57 mL, 109 mmol) and DMF (2 drops), and the resulting mixture was stirred at room temperature until gas evolution ceased. The mixture was concentrated and dried in vacuo. In a separate, heat-dried reaction flask a mixture of ZnBr2 (24.6 g, 109 mmol) in anhydrous THF (300 mL) at −78° C. was added a solution of CH3MgBr (29.1 mL, 3.0 M in Et2O, 87 mmol) dropwise. The resulting mixture was stirred at −78° C. for 15 minutes, and then the reaction mixture was allowed to warm to room temperature and stirred for 30 minutes. The mixture was cooled to −78° C. and a solution of the acid chloride in anhydrous THF (100 mL) was added dropwise, followed by Pd(PPh3)4 (1.68 g, 1.46 mmol). The resulting mixture was allowed to stir at −78° C. for 10 minutes, and was then allowed to warm to ambient temperature and stirred for an additional 16 hours. The mixture was quenched by adding aq. 1 M HCl, diluted with H2O (100 mL), and extracted with CH2Cl2 (3×300 mL). The combined organic extracts were dried (MgSO4), filtered and concentrated. The crude product was purified by column chromatography (silica gel, 5% EtOAc in hexanes) to afford the title compound (11.79 g, 74%).

Workup

  1. concentrationThe mixture was concentrated
  2. customdried in vacuo
  3. customIn a separate, heat-dried
  4. customreaction flask
  5. stirringThe resulting mixture was stirred at −78° C. for 15 minutes
  6. temperatureto warm to room temperature
  7. stirringstirred for 30 minutes
  8. temperatureThe mixture was cooled to −78° C.
  9. stirringto stir at −78° C. for 10 minutes
  10. temperatureto warm to ambient temperature
  11. stirringstirred for an additional 16 hours
  12. customThe mixture was quenched
  13. additionby adding aq. 1 M HCl
  14. additiondiluted with H2O (100 mL)
  15. extractionextracted with CH2Cl2 (3×300 mL)
  16. dry with materialThe combined organic extracts were dried (MgSO4)
  17. filtrationfiltered
  18. concentrationconcentrated
  19. customThe crude product was purified by column chromatography (silica gel, 5% EtOAc in hexanes)

Sources & evidence

ORD record
ord-2d86d6e0ae5c47169ca911629dbd2c61
Source dataset
uspto-grants-2015_01
Patent number
US08937150B2

Reaction notes

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