Phosphorus oxychloride → 2-Chloro-5-fluoro-1,3-benzoxazole

HRID 1597827Notes

Reaction equation

HRID 1597827 reaction equation
S[C:2]1[O:3][C:4]2[CH:10]=[CH:9][C:8]([F:11])=[CH:7][C:5]=2[N:6]=1.O=P(Cl)(Cl)[Cl:14].P(Cl)(Cl)(Cl)(Cl)Cl>C(Cl)Cl>[Cl:14][C:2]1[O:3][C:4]2[CH:10]=[CH:9][C:8]([F:11])=[CH:7][C:5]=2[N:6]=1

Participants

5

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 24819Phosphorus pentachlorideHCID 178505481HCID 178505481, compound

Product 1

HCID 141698172-Chloro-5-fluoro-1,3-benzoxazoleYield 86.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The 2-mercapto-5-fluorobenzoxazole (2.0 g, 11.8 mmol) is slurried into POCl3 (9.7 mL, 104 mmol). The slurry is treated with PCl5 (3.0 g, 14.2 mmol) and 5.0 mL of anhydrous CH2Cl2. The mixture is stirred at room temperature for 5.5 hours. After this time excess POCl3 is removed under reduced pressure. The residue is treated with saturated aqueous NaHCO3 and the mixture is poured into a separatory funnel. The mixture is extracted with EtOAc and the combined extracts are washed with brine and dried over anhydrous Na2SO4. Filtration and concentration gives 1.76 g of 2-chloro-5-fluorobenzoxazole as a waxy solid. The crude chloride is used in the piperazine displacement reaction.

Workup

  1. customAfter this time excess POCl3 is removed under reduced pressure
  2. additionThe residue is treated with saturated aqueous NaHCO3
  3. additionthe mixture is poured into a separatory funnel
  4. extractionThe mixture is extracted with EtOAc
  5. washthe combined extracts are washed with brine
  6. dry with materialdried over anhydrous Na2SO4
  7. filtrationFiltration and concentration

Sources & evidence

ORD record
ord-3c34cdba3dca4b46bff2d79cedf42c8c
Source dataset
uspto-grants-1998_04
Patent number
US05736545

Reaction notes

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