反応 #41793

反応方程式

4-fluorophenylisothiocyanate

4-(3-Amino-4-methylamino-phenoxy)-pyridine-2-carboxylic acid tert-butyl ester

→

desired product

4-[2-(4-Fluoro-phenylamino)-1-methyl-1H-benzoimidazol-5-yloxy]-pyridine-2-carboxylic acid tert-butyl ester

溶媒

MeOH

反応条件

後処理

1. 1
   温度The reaction was maintained
2. 2
   workup.STIRRINGthe resulting mixture was stirred overnight
3. 3
   その他The reaction was partitioned with EtOAc and water
4. 4
   ろ過filtered through Celite
5. 5
   その他The layers were separated
6. 6
   抽出The resulting aqueous phase was extracted with EtOAc
7. 7
   ろ過the mixture was filtered through Celite
8. 8
   その他The phases were separated
9. 9
   抽出the aqueous phase was again extracted
10. 10
    ろ過filtered
11. 11
    洗浄The combined organic layers were washed with brine
12. 12
    乾燥dried over MgSO4
13. 13
    ろ過filtered
14. 14
    濃縮concentrated
15. 15
    その他to give a brown solid
16. 16
    その他The crude residue was purified by trituration in hot toluene

実験手順

A round bottom flask was charged with 4-fluorophenylisothiocyanate (1 eq), 4-(3-Amino-4-methylamino-phenoxy)-pyridine-2-carboxylic acid tert-butyl ester (1 eq), and MeOH. The reaction was maintained stirring at room temperature overnight. Ferric chloride, (1.5 eq) was added and the resulting mixture was stirred overnight. The reaction was partitioned with EtOAc and water, and filtered through Celite. The layers were separated and the aqueous phase was neutralized with saturated Na2CO3 solution. The resulting aqueous phase was extracted with EtOAc and the mixture was filtered through Celite. The phases were separated and the aqueous phase was again extracted and filtered. The combined organic layers were washed with brine, dried over MgSO4, filtered, and concentrated to give a brown solid. The crude residue was purified by trituration in hot toluene to furnish the desired product. LCMS m/z 435.6 (MH+), tR=2.12 min.

出典