Dimethylformamide → Methyl 4-bromo-5-formylfuran-2-carboxylate

A solution of 69.65 g (0.246 mol) of methyl 4,5-dibromo-2-furoate in 700 mL of dry THF was cooled to −45° C. under argon. To this solution 141.5 mL (0.282 mol) of isopropyl magnesium chloride 2M (Aldrich) was slowly added over 45 min at −43/−48° C. and the mixture was stirred for an additional hour. The resulting suspension was treated dropwise with 56.8 mL (0.737 mol) of anhydrous DMF (Aldrich, H2O<0.005%) over 30 min at −45° C. and stirred for 15 min at the same temperature. The reaction mixture was slowly warmed to +20° C., stirred for 1 hour and then it was slowly poured in a mixture of 1.2 L of HCl 1 M and 1.0 L of MTBE. The aqueous layer was separated and extracted twice with 1.0 L and 0.5 L of MTBE. The combined organic extracts were concentrated to dryness affording 57.81 g of crude material, which was crystallized from 120 mL of hot toluene and 230 mL of n-heptane. The resulting slurry was cooled to +4° C., aged for 2 h and filtered to afford 46.55 g of beige solid.

1. stirringstirred for 15 min at the same temperature
2. temperatureThe reaction mixture was slowly warmed to +20° C.
3. stirringstirred for 1 hour
4. customThe aqueous layer was separated
5. extractionextracted twice with 1.0 L and 0.5 L of MTBE
6. concentrationThe combined organic extracts were concentrated to dryness
7. customaffording 57.81 g of crude material, which
8. customwas crystallized from 120 mL of hot toluene and 230 mL of n-heptane
9. temperatureThe resulting slurry was cooled to +4° C.
10. filtrationfiltered

ORD record

ord-39207de22879488d834f4ebe7f8e1fa9

Source dataset

uspto-grants-2009_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07485661B2