Reaktion #69375

Reaktionsgleichung

methylamine

3,5-difluoro-4-formylbenzoic acid

oxalyl chloride

HCl

→

title compound

Ausbeute 80.2%

3,5-difluoro-4-formyl-N-methylbenzamide

Ausbeute 80.2%

Lösungsmittel

dichloromethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigean internal temperature of 10° C
2. 2
   workup.STIRRINGstirred for an additional 1.5 hr
3. 3
   TemperaturThe solution was then cooled to 0° C.
4. 4
   Sonstigean internal temperature of 7° C
5. 5
   Temperaturwarmed to room temperature
6. 6
   SonstigeThe organic layer was separated
7. 7
   Waschenwashed with brine (500 mL)
8. 8
   Trocknendried over MgSO4
9. 9
   Filtrationfiltered
10. 10
    Einengenconcentrated under vacuum
11. 11
    Temperaturthe resulting mixture was heated
12. 12
    Temperaturto reflux for 0.5 hr
13. 13
    Temperaturcooled to room temperature
14. 14
    workup.STIRRINGstirred for 18 hr
15. 15
    TemperaturAfterward, the mixture was cooled to 0° C.
16. 16
    Filtrationfiltered
17. 17
    Waschenrinsed with pentane
18. 18
    Sonstigedried under vacuum

Vorschrift

To an ice-cold solution of 3,5-difluoro-4-formylbenzoic acid (120 g, 645 mmol) in dichloromethane (1.5 L) and N,N-dimethylformamide (2.0 g, 27 mmol) was added oxalyl chloride (90 g, 709 mmol) drop-wise at a rate that allowed the mixture to not exceed an internal temperature of 10° C. The resulting mixture was stirred at the same temperature for 0.5 hr, warmed to room temperature, and stirred for an additional 1.5 hr. The solution was then cooled to 0° C., and aqueous methylamine (40%, 168 mL, 1.94 mol) was added drop-wise at a rate that allowed the mixture to not exceed an internal temperature of 7° C. Afterward, the mixture was quenched with aqueous HCl (2M, 335 mL, 670 mmol) and warmed to room temperature. The organic layer was separated, washed with brine (500 mL), dried over MgSO4, filtered, and concentrated under vacuum. The resulting residual solid was taken in MTBE (500 mL), and the resulting mixture was heated to reflux for 0.5 hr, cooled to room temperature, and stirred for 18 hr. Afterward, the mixture was cooled to 0° C., filtered, rinsed with pentane, and dried under vacuum to form the title compound (103 g, 80%) as a solid. 1H NMR (300 MHz, CDCl3) δ ppm 3.03 (d, J=4.86 Hz, 3H), 6.37 (br s, 1H), 7.36-7.42 (m, 2H), 10.36 (s, 1H); MS m/z 200.06 [M+H]+ (ESI).

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