Reaktion #49053

Reaktionsgleichung

tert-Butyl carbamate

trifluoroacetic acid

triethylsilane

3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-5-formyl-benzoic acid

3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-5-formyl-benzoic acid

→

5-(tert-butoxycarbonylamino-methyl)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzoic acid

Lösungsmittel

acetonitrile

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeAfter completion of the reaction
2. 2
   Sonstigethe reaction mixture was evaporated under reduced pressure
3. 3
   Extraktionthe resultant residue was extracted with ethyl acetate
4. 4
   WaschenThe organic layer was washed sequentially with water and saturated brine
5. 5
   Trocknendried over anhydrous sodium sulfate
6. 6
   Sonstigeevaporated under reduced pressure
7. 7
   SonstigeThe resultant crude product was purified by silica gel flash chromatography (Mega Bond Elut, Varian, 5% methanol/methylene chloride as an eluent)

Vorschrift

tert-Butyl carbamate (commercially available, 187 mg, 1.602 mmol), trifluoroacetic acid (123 μL, 1.602 mmol), and triethylsilane (255 μL, 1.602 mmol) were added sequentially to a suspension of 3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-5-formyl-benzoic acid (225 mg, 0.534 mmol) obtained in Step A of Example 5 in acetonitrile (anhydrous, 20 mL). The mixture was stirred at room temperature for 5 days. After completion of the reaction, the reaction mixture was evaporated under reduced pressure, and the resultant residue was extracted with ethyl acetate. The organic layer was washed sequentially with water and saturated brine, dried over anhydrous sodium sulfate, and evaporated under reduced pressure. The resultant crude product was purified by silica gel flash chromatography (Mega Bond Elut, Varian, 5% methanol/methylene chloride as an eluent) to give 5-(tert-butoxycarbonylamino-methyl)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzoic acid. [LC/MS m/z 523 (M+1)]. Then, trifluoroacetic acid (0.5 mL) was added to a solution of the resultant product in methylene chloride (20 mL), and the mixture was stirred at room temperature for 14 hours. After completion of the reaction, the reaction mixture was evaporated under reduced pressure, and the resultant residue was recrystallized from a mixed solvent of diethyl ether:hexane (1:1) to give 5-aminomethyl-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzoic acid trifluoroacetate (285 mg, 99% in 2 steps) as white crystals.

Quelle