2-(bromomethyl)-4-(trifluoromethyl)furan

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2.95 g of the product of Stage E, 9 ml of water and 3.6 g of hexamethylenetetramine were refluxed for 1 hour. 9 ml of concentrated hydrochloric acid were added. Reflux was maintained for an additional 1 hour and the mixture was allowed to return to room temperature, diluted with water and extracted with methylene chloride. The extract was washed with water and dried and the solvent was evaporated to obtain 1.9 g of the expected product. Reflux was maintained for an additional 1 hour to return to room temperature extracted with methylene chloride The extract was washed with water dried the solvent was evaporated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 6 g of the product of Stage D were refluxed for 1 and a half hours in 50 ml of carbon tetrachloride in the presence of 7.2 g of N-bromosuccinimide and 0.3 g of azobisisobutyronitrile and the mixture was allowed to return to room temperature and was filtered. The solvent was evaporated and the residue was chromatographed on silica (eluent: 98/2 ether/isopropyl ether) to obtain 5.5 g of the expected product. to return to room temperature was filtered The solvent was evaporated the residue was chromatographed on silica (eluent: 98/2 ether/isopropyl ether)

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-bromomethyl-4-trifluoromethyl-furan (500 mg, 3.57 mmol), hexamethylenetetramine (HMTA) (637 mg, 4.54 mmol) and water (2.6 mL) were placed in a 50 mL pear-shaped flask equipped with a vigreaux column atop of which is attached to dry-ice condenser chilled at −78° C. The mixture was heated at reflux for 1 h, and then treated with concentrated HCl (1.7 mL). Reflux was maintained for an additional 1 h before the reaction was cooled to rt, diluted with water and extracted with DCM (4×50 mL). The combined organic extracts were washed with water, brine, dried (Na2SO4) and carefully concentrated to give 4-(trifluoromethyl)furan-2-carbaldehyde. 1H NMR (400 MHz, CDCl3) δ ppm 7.37 (m, 1H), 8.01 (m, 1H), 9.74 (d, J=0.54 Hz, 1H). were placed in a 50 mL pear-shaped flask equipped with a vigreaux column atop of which is attached to dry-ice condenser The mixture was heated at reflux for 1 h Reflux was maintained for an additional 1 h before the reaction was cooled to rt extracted with DCM (4×50 mL) The combined organic extracts were washed with water, brine dried (Na2SO4) carefully concentrated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 2-methyl-4-trifluoromethyl-furan (J. Heterocyclic Chemistry 1970, 7, 269-272) (340 mg, 2.26 mmol), N-bromosuccinimide (423 mg, 2.38 mmol) and azobisisobutyronitrile (19 mg, 0.11 mmol) in carbon tetrachloride (10 mL) was refluxed for 1.5 h, then allowed to cool to rt and filtered through a cotton plug. The solvent was evaporated to give 2-(bromomethyl)-4-(trifluoromethyl)furan as an orange oil (508 mg, 98%). The product was pure enough by proton NMR that no further purification was necessary. 1H NMR (400 MHz, CDCl3) δ ppm 4.46 (d, J=0.44 Hz, 2H), 6.56 (d, J=0.49 Hz, 1H), 7.77 (m, 1H). filtered through a cotton plug The solvent was evaporated