Phosphorus oxybromide → HCID 11368839, compound

Temperature

65 °C

To a 1-Liter 3-neck flask was charged 50 g (0.26 mol) of 2-(4-fluorophenyl)-1,3-cyclopentanedione as a solid to 260 mL of dry MeCN (KF<100 ug/mL). To the resulting suspension was added 18.5 g (0.13 mol) of Na2HPO4 and the sides of the reaction flask were washed with an additional 100 ml of dry MeCN. In a separate flask containing 150 mL of MeCN was added 56 g (0.195 mol) of POBr3. The resulting POBr3 solution was then added drop-wise to the slurry, and the mixture was heated to 65° C. for 1.5 h and cooled to rt. The reaction mixture was quenched with 1N KOH to a final pH of <8.0 and aged for 30 min. During the quench the precipitation of insolubles occurs at pH<4 which turns to an oily mass around pH 7-7.5. The bottom oily layer and aqueous layer were separated. The top MeCN layer containing the product was filtered over a small plug of solka floc, which was then rinsed with one bed volume of MeCN. The combined MeCN layers were then concentrated to a final volume of 500 mL. To the concentrated solution was added 600 mL of water at rt and the mixture seeded with 500 mg of 3-bromo-2-(4-fluorophenyl)-2-cyclopenten-1-one. After aging for 30 min, the remaining 700 mL of water were added drop-wise. After 45 min, the slurry was filtered, washed with 100 mL of water and dried under vacuum at 25° C. giving 3-bromo-2-(4-fluorophenyl)-2-cyclopenten-1-one as a light brown solid.

1. washthe sides of the reaction flask were washed with an additional 100 ml of dry MeCN
2. additionIn a separate flask containing 150 mL of MeCN
3. temperaturecooled to rt
4. customThe reaction mixture was quenched with 1N KOH to a final pH of <8.0
5. customDuring the quench
6. customthe precipitation of insolubles
7. customThe bottom oily layer and aqueous layer were separated
8. additionThe top MeCN layer containing the product
9. filtrationwas filtered over a small plug of solka floc, which
10. washwas then rinsed with one bed volume of MeCN
11. concentrationThe combined MeCN layers were then concentrated to a final volume of 500 mL
12. additionTo the concentrated solution was added 600 mL of water at rt
13. waitAfter aging for 30 min
14. additionthe remaining 700 mL of water were added drop-wise
15. waitAfter 45 min
16. filtrationthe slurry was filtered
17. washwashed with 100 mL of water
18. customdried under vacuum at 25° C.

ORD record

ord-6a6f45cfcf984dfbb2fc9ddc61e2e45b

Source dataset

uspto-grants-2011_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07893091B2