Dimethylformamide → 2,3-Difluoro-6-methoxybenzaldehyde

Temperature

-55 °C

A solution of 1,2-difluoro-4-methoxy-benzene (Aldrich; 10.0 g, 69.4 mmol) in dry tetrahydrofuran (500 mL) was cooled to −78° C. under a nitrogen atmosphere. A solution of lithium diisopropylamide (available from Aldrich Chemical Company, Inc., 1001 West Saint Paul Avenue, Milwaukee, Wis. 53233, USA; 1.8 M in tetrahydrofuran/heptane/ethylbenzene, 40 mL, 72.9 mmol) was added dropwise by syringe. The reaction mixture was warmed to −55° C. and held at this temperature for 1 h. The mixture was then cooled again to −78° C., and dry N,N-dimethylformamide (10.7 mL, 139 mmol) was added by syringe. The cooling bath was removed and the reaction was allowed to warm to −10° C. and quenched by the addition of ice flakes (˜200 mL) and a solution of saturated ammonium chloride (200 mL). Ethyl acetate (200 mL) was added, the layers were separated and the aqueous later was extracted with ethyl acetate (200 mL). The combined organic layers were washed with brine, dried over sodium sulfate, filtered, evaporated, and purified by silica gel chromatography, eluting with 0-30% ethyl acetate/hexanes to give 2,3-difluoro-6-methoxy-benzaldehyde (7.0 g, 59% yield) as an oil that solidified upon standing.

1. temperatureThe mixture was then cooled again to −78° C.
2. customThe cooling bath was removed
3. temperatureto warm to −10° C.
4. customquenched by the addition of ice flakes (˜200 mL)
5. additionEthyl acetate (200 mL) was added
6. customthe layers were separated
7. extractionthe aqueous later was extracted with ethyl acetate (200 mL)
8. washThe combined organic layers were washed with brine
9. dry with materialdried over sodium sulfate
10. filtrationfiltered
11. customevaporated
12. custompurified by silica gel chromatography
13. washeluting with 0-30% ethyl acetate/hexanes

ORD record

ord-88df4876325b4fa6a5a01ca2c420afba

Source dataset

uspto-grants-2012_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08314250B2