Bromide ion → HCID 11481706, compound

Temperature

60 °C

To 50 mL of dry dimethylacetamide (DMAC, KF<100 ug/mL) was added 25 g (98 mmol) of 3-bromo-2-(4-fluorophenyl)-2-cyclopenten-1-one as a solid. In a separate 100 mL round-bottom flask was mixed 2.08 g of 5% Pd/C and 40 mL of DMAC. The slurry containing the catalyst was then added to the flask containing the starting bromide and the 100 mL round bottom flask rinsed with an additional 10 mL DMAC. To the reaction mixture was then added 46.7 mL (196 mmol) of N-tributylamine and 20 mL (473 mmol) of MeOH. The resulting reaction flask was purged with nitrogen (5×) and then with CO (5×). The CO pressure was set at 10 psi and the reaction mixture heated at 60° C. for 12 h. The reaction mixture was filtered over a small plug of solka floc to remove the catalyst and the pad washed with MeOH (172 mL). The methanol was removed under reduced pressure. To the mixture was slowly added 8.6 mL of 1N HCl at such a rate to keep the temperature <24° C., and then the batch was seeded with 1 wt % of methyl 2-(4-fluorophenyl)-3-oxo-1-cyclopent-1-enecarboxylate. After aging for 15 min, 163 mL of 1N HCl was added drop-wise over the next 2.5 hours maintaining the temperature <25° C. The slurry was aged at 15-20° C. for 30 min and sampled for supernatant concentration and filtered. The cake is washed with 17 mL of 1 N HCl and then water until the pH of the filtrate was >5. The product is dried under vacuum/nitrogen sweep for 40 h at 25° C. to give methyl 2-(4-fluorophenyl)-3-oxo-1-cyclopent-1-enecarboxylate as a brown solid.

1. additionThe slurry containing the catalyst
2. additionwas then added to the flask
3. washthe 100 mL round bottom flask rinsed with an additional 10 mL DMAC
4. customThe resulting reaction flask
5. customwas purged with nitrogen (5×)
6. filtrationThe reaction mixture was filtered over a small plug of solka floc
7. customto remove the catalyst
8. washthe pad washed with MeOH (172 mL)
9. customThe methanol was removed under reduced pressure
10. customthe temperature <24° C.
11. addition163 mL of 1N HCl was added drop-wise over the next 2.5 hours
12. temperaturemaintaining the temperature <25° C
13. waitThe slurry was aged at 15-20° C. for 30 min
14. aliquotsampled for supernatant concentration
15. filtrationfiltered
16. washThe cake is washed with 17 mL of 1 N HCl
17. customThe product is dried under vacuum/nitrogen sweep for 40 h at 25° C.

ORD record

ord-b6da88f29f4d436985aaa4322ffddd94

Source dataset

uspto-grants-2011_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07893091B2