반응 #537654

반응 방정식

1-chloropyrrolidine-2,5-dione

Acetaldoxime

triethylamine

4-(2-ethynylpyridin-4-yloxy)-2-fluorobenzenamine

acetaldoxime

1-chloropyrrolidine-2,5-dione

→

2-fluoro-4-(2-(3-methylisoxazol-5-yl)pyridin-4-yloxy)benzenamine

수율 23.1%

용매

THF

EtOAc

water

반응 조건

후처리

1. 1
   온도the reaction heated for an additional 45 min at 130° C
2. 2
   기타The organic layer was separated
3. 3
   추출the aqueous layer was extracted with EtOAc (2×20 ml)
4. 4
   세척The combined organics were washed with brine
5. 5
   건조dried (Na2SO4)
6. 6
   농축concentrated in vacuo
7. 7
   기타purified by column chromatography (EtOAc-hexanes)

실험 절차

Acetaldoxime (0.078 g, 1.321 mmol) and triethylamine (0.246 ml, 1.761 mmol) were added to a solution of 4-(2-ethynylpyridin-4-yloxy)-2-fluorobenzenamine (0.201 g, 0.881 mmol) in THF (4 mL) in a microwave reaction vial. To this solution was added 1-chloropyrrolidine-2,5-dione (0.176 g, 1.32 mmol) and the mixture was stirred at 130° C. for 45 min under microwave irradiation. An additional 1.5 eq each of acetaldoxime and 1-chloropyrrolidine-2,5-dione were added and the reaction heated for an additional 45 min at 130° C. This process was repeated one more time. The mixture was poured into a biphasic solution of water (40 mL) and EtOAc (30 mL). The organic layer was separated and the aqueous layer was extracted with EtOAc (2×20 ml). The combined organics were washed with brine, dried (Na2SO4), concentrated in vacuo and purified by column chromatography (EtOAc-hexanes) to afford 2-fluoro-4-(2-(3-methylisoxazol-5-yl)pyridin-4-yloxy)benzenamine (58 mg, 23% yield) as light red colored residue. MS (ESI) m/z: 286.1 (M+H+).

출처