Phosphorus oxychloride → 3-Chloro-6,7-difluorobenzo[d]isoxazole

Temperature

140 °C

TEA (5.6 ml, 40.2 mmol) was added to an ice bath cooled mixture of 6,7-difluoro-1,2-benzisoxazol-3(2H)-one (Intermediate 528, 6.88 g, 40.2 mmol) and POCl3 (13.1 ml, 141 mmol) (exotherm results) in a microwave reactor vessel and the mixture was heated at 140° C. for 6 hours in a microwave reactor. The mixture was taken up in ether and washed with Na2CO3 (2×) and brine. The combined aqueous layers were twice more extracted with ether, which was washed with Na2CO3 and brine. The combined ether layers were dried (MgSO4) and concentrated to give an oil that slowly solidified. The material was chromatographed on silica gel (hexanes followed by gradient elution to 50% CH2Cl2 in hexanes) to afford 5.64 g of product as an off-white solid.

1. temperaturecooled
2. washwashed with Na2CO3 (2×) and brine
3. extractionThe combined aqueous layers were twice more extracted with ether, which
4. washwas washed with Na2CO3 and brine
5. dry with materialThe combined ether layers were dried (MgSO4)
6. concentrationconcentrated
7. customto give an oil that
8. customThe material was chromatographed on silica gel (hexanes followed by gradient elution to 50% CH2Cl2 in hexanes)

ORD record

ord-c8259fcb39754015923f695eaa5135c1

Source dataset

uspto-grants-2015_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09040528B2