2,4-Dibromo-1-(methoxymethoxy)benzene → 2-(5-Bromo-alpha-hydroxy-2-methoxymethoxybenzyl)-3-fluoropyridine

To a solution of 2,4-dibromo-1-methoxymethoxybenzene (3.50 g) in diethyl ether (50 ml) was added, at -78° C. under argon atmosphere, a 1.6M n-butyl lithium hexane solution (8.1 ml). The mixture was stirred for 20 minutes at the same temperature, to which was added a solution of 3-fluoro-2-formyl-pyridine (1.48 g) in THF (10 ml), followed by stirring for one hour at temperatures ranging from -78° to 60° C. The reaction mixture was poured into a saturated aqueous saline solution, followed by extraction with ethyl acetate. The extract solution was washed with a saturated aqueous saline solution, dried (anhydrous sodium sulfate) and concentrated. The concentrate was purified by means of a silica gel column chromatography (eluent: ethyl acetate/hexane) to give 2-(5-bromo-α-hydroxy-2-methoxymethoxybenzyl)-3-fluoropyridine (1.64 g) (Compound D-6). The physical properties and spectrum data are shown in Table 13 and Table 14.

1. stirringby stirring for one hour at temperatures
2. customranging from -78° to 60° C
3. additionThe reaction mixture was poured into a saturated aqueous saline solution
4. extractionfollowed by extraction with ethyl acetate
5. washThe extract solution was washed with a saturated aqueous saline solution
6. dry with materialdried (anhydrous sodium sulfate)
7. concentrationconcentrated
8. customThe concentrate was purified by means of a silica gel column chromatography (eluent: ethyl acetate/hexane)

ORD record

ord-6a10384d381e4f25b4d335e71c48b3c1

Source dataset

uspto-grants-1998_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05716971