Toluene → 2-Fluoro-3-methoxybenzaldehyde

Temperature

-78 °C

To a solution of 2-fluoro-3,N-dimethoxy-N-methyl-benzamide (2.30 g, 10.8 mmol) in THF (20 mL) at −78° C. was added 1M DIBAL-H in toluene (12 mL, 12 mmol). The reaction stirred at −78° C. for 3 h and then the remaining 1M DIBAL-H in toluene (4.2 mL, 4.2 mmol) was added to the reaction. The reaction was allowed to stir at −78° C. for 30 min and was then warmed to rt. The reaction was quenched slowly with saturated aqueous NH4Cl. The organic phase was separated and the aqueous phase was extracted with 2×50 mL ethyl acetate. The combined organic phases were washed successively with 1N HCl and brine. The organic phase was dried (MgSO4) and concentrated in vacuo. The residue was purified by flash chromatography eluting silica gel with EtOAc:hexane [0:100 to 1:1] to yield the title compound (1.41 g, 85%): δH (300 MHz, CDCl3): 10.38 (1H, s), 7.43-7.40 (1H, m), 7.24-7.15 (2H, m), 3.95 (3H, s).

1. stirringto stir at −78° C. for 30 min
2. temperaturewas then warmed to rt
3. customThe reaction was quenched slowly with saturated aqueous NH4Cl
4. customThe organic phase was separated
5. extractionthe aqueous phase was extracted with 2×50 mL ethyl acetate
6. washThe combined organic phases were washed successively with 1N HCl and brine
7. dry with materialThe organic phase was dried (MgSO4)
8. concentrationconcentrated in vacuo
9. customThe residue was purified by flash chromatography
10. washeluting silica gel with EtOAc

ORD record

ord-a51bace08a9a44578ff9ef881a83eb21

Source dataset

uspto-grants-2008_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07417064B2