2-Amino-3-Difluoromethoxy-5-Bromopyridine

2-bromo-5-hydroxy-4-methoxy benzoic acid (B13); 1 Kg of 2-bromo-5-hydroxy-4-methoxy benzaldehyde (B2) and 1.255 Kg of sulfamic acid were added with stirring into a mixture of 4.473 Kg of EtOAc and 8 L of water. The reaction mixture was stirred until all of the solid had dissolved. The reaction mixture was cooled to between -10 and 0° C. An aqueous solution of sodium chlorite was prepared by dissolving 505 g of sodium chlorite in 3 L of water. The sodium chlorite solution was added to the pre-cooled B2 solution at a rate that maintained the reaction temperature under 5° C. After the complete addition of sodium chlorite solution, the reaction mixture was stirred for another hour at 0° C. and was then allowed to warm up to room temperature. The reaction was monitored by TLC. After the TLC analysis showed completion of the reaction, the aqueous layer was separated. The aqueous layer was extracted with EtOAc (1.789 Kg) and the combined organic layer was transferred to another flask and EtOAc was removed by vacuum distillation at 40° C. 6.92 Kg of toluene was added at between 30 to 40° C., the slurry was cooled to between -10 to 0° C. and the precipitate was collected by filtration to give about 950 g (89percent (wt?)yield) of 2-bromo-5-hydroxy-4-methoxy benzoic acid (B13). 2-bromo-5-hydroxy-4-methoxy benzoic acid (B13); 1 Kg of 2-bromo-5-hydroxy-4-methoxy benzaldehyde (B2) and 1.255 Kg of sulfamic acid were added with stirring into a mixture of 4.473 Kg of EtOAc and 8 L of water. The reaction mixture was stirred until all of the solid had dissolved. The reaction mixture was cooled to between -10 and 0° C. An aqueous solution of sodium chlorite was prepared by dissolving 505 g of sodium chlorite in 3 L of water. The sodium chlorite solution was added to the pre-cooled B2 solution at a rate that maintained the reaction temperature under 5° C. After the complete addition of sodium chlorite solution, the reaction mixture was stirred for another hour at 0° C. and was then allowed to warm up to room temperature. The reaction was monitored by TLC. After the TLC analysis showed completion of the reaction, the aqueous layer was separated. The aqueous layer was extracted with EtOAc (1.789 Kg) and the combined organic layer was transferred to another flask and EtOAc was removed by vacuum distillation at 40° C. 6.92 Kg of toluene was added at between 30 to 40° C., the slurry was cooled to between -10 to 0° C. and the precipitate was collected by filtration to give about 950 g (89percent (wt?)yield) of 2-bromo-5-hydroxy-4-methoxy benzoic acid (B13).

Molecular Weight:247.04
XLogP3:1.8
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:2
Exact Mass:245.95277
Monoisotopic Mass:245.95277
Topological Polar Surface Area:66.8
Heavy Atom Count:13
Complexity:197
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes