반응 #73402

반응 방정식

bromomethyl acetate

acetoxymethylzinc bromide

NH4Cl

1,2-Dibromoethane

5-(2-chloropyrimidin-4-yloxy)-4-fluoro-2-methyl-1H-indole

S-phos

TMSCl

→

(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)pyrimidin-2-yl)methyl acetate

용매

DMF

DMF

반응 조건

후처리

1. 1
   온도cooled to room temperature
2. 2
   기타the resulting mixture is sonicated for 30 min
3. 3
   기타the supernatant is removed by syringe
4. 4
   workup.ADDITIONDMF (8 mL) is added
5. 5
   workup.STIRRINGThe resulting mixture is stirred at 23° C. for 15 h
6. 6
   기타the mixture is then partitioned between EtOAc (150 mL) and water (150 mL)
7. 7
   추출The aqueous layer is extracted with EtOAc (2×100 mL)
8. 8
   세척The combined organic layers are washed with brine (60 mL)
9. 9
   건조dried (Na2SO4)
10. 10
    농축concentrated
11. 11
    기타The residue is purified by silica gel chromatography (0-100% EtOAc/heptane)

실험 절차

1,2-Dibromoethane (425 μL, 5.0 mmol) is added to a suspension of zinc powder (2.83 g, 43.2 mmol) in dry DMF (8 mL). The reaction mixture is heated at 60° C. for 10 min, then cooled to room temperature. TMSCl (500 μl, 4.0 mmol) is added (caution: exothermic!) and the resulting mixture is sonicated for 30 min. Zinc powder is allowed to settle and the supernatant is removed by syringe. DMF (8 mL) is added, followed by bromomethyl acetate (2.12 mL, 21.61 mmol). The mixture is stirred at 23° C. for 2.5 h. Zinc is allowed to settle and the solution of acetoxymethylzinc bromide is then transferred to a solution of 5-(2-chloropyrimidin-4-yloxy)-4-fluoro-2-methyl-1H-indole (2.00 g, 7.20 mmol), palladium acetate (0.081 g, 0.360 mmol), and S-phos (0.355 g, 0.864 mmol) in DMF (10 mL) at 23° C. The resulting mixture is stirred at 23° C. for 15 h. Saturated aqueous NH4Cl (100 mL) is added and the mixture is then partitioned between EtOAc (150 mL) and water (150 mL). The aqueous layer is extracted with EtOAc (2×100 mL). The combined organic layers are washed with brine (60 mL), dried (Na2SO4), and concentrated. The residue is purified by silica gel chromatography (0-100% EtOAc/heptane) to give (4-(4-fluoro-2-methyl-1H-indol-5-yloxy)pyrimidin-2-yl)methyl acetate.

출처