2,4-Difluorobenzaldehyde → HCID 67257315, compound

Temperature

0 °C

To a mixture of 5-bromo-2-methoxypyridine 1 (2.10 g, 10.6 mmol) in anhydrous TBME (20 ml) at −32° C. under argon atmosphere was added n-BuLi solution (5.8 ml of 2 M solution in cyclohexane, 11.7 mmol) drop wise over 15 min under argon condition. After stirring for 1 h, 2,4-difluorobenzaldehyde (1.54 g, 10.6 mmol) was added drop wise over 15 min and the reaction mixture was stirred for 30 min under −32° C. under argon atmosphere. Reaction mixture was allowed to warm up to 0° C. and quenched with saturated NH4Cl (20 ml). The phases were separated and the aqueous layer was extracted with TBME (20 ml and 10 ml). All combined organic phases were washed with water (50 ml), and dried over anhydrous sodium sulfate. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography on silica gel (hexanes:ethyl acetate, 85:15). Yield 2.28 g (850%). 1H NMR (CDCl3, 500 MHz): δ 8.16 (s, 1H), 7.57-7.52 (m, 2H), 6.93-6.76 (m, 2H), 6.72 (d, 1H, J=9.0 Hz), 6.07 (d, 1H, J=3.5 Hz), 3.92 (s, 3H). 13C NMR (CDCl3, 125 MHz): δ 163.9, 162.4, 159.6, 145.0, 137.2, 131.0, 128.2, 126.5, 111.5, 110.9, 103.9, 67.3, 53.6.

1. stirringthe reaction mixture was stirred for 30 min under −32° C. under argon atmosphere
2. customReaction mixture
3. customquenched with saturated NH4Cl (20 ml)
4. customThe phases were separated
5. extractionthe aqueous layer was extracted with TBME (20 ml and 10 ml)
6. washAll combined organic phases were washed with water (50 ml)
7. dry with materialdried over anhydrous sodium sulfate
8. customThe solvent was evaporated in vacuo
9. customthe residue was purified by flash column chromatography on silica gel (hexanes:ethyl acetate, 85:15)

ORD record

ord-ef4fddf72d3040d18f42c6ba84c3cda6

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08703801B2