반응 #41408

반응 방정식

(αS)-3-Fluoro-β-[[1-(4-fluorophenyl)-1H-indazole-5-yl]oxy]-α-(2-methylpropyl)benzeneethanamine

Triethylamine

2-methoxyacetyl chloride

→

N-{(1S)-1-[(S)-(3-fluorophenyl)-{[1-(4-fluorophenyl)-1H-indazole-5-yl]oxy}methyl}-3-methyl-butyl}-2-methoxyacetamide

수율 68.0%

용매

dichloromethane

dichloromethane

반응 조건

후처리

1. 1
   세척washed with water and brine
2. 2
   건조dried over Na2SO4
3. 3
   여과After filtration the solvent
4. 4
   기타is evaporated
5. 5
   기타the residue is purified by chromatography (silicagel, eluents: ethylacetate/hexane)
6. 6
   workup.ADDITIONThe obtained mixture of the two stereoisomers
7. 7
   기타is separated by HPLC (Chiralpak AD-H 5 μm, eluents: hexane/ethanol)

실험 절차

(αS)-3-Fluoro-β-[[1-(4-fluorophenyl)-1H-indazole-5-yl]oxy]-α-(2-methylpropyl)benzeneethanamine (76.4 mg, 0.18 mmol) is dissolved in 7 mL dichloromethane. Triethylamine (0.06 mL, 0.44 mmol) and 2-methoxyacetyl chloride (0.02 mL, 0.22 mmol) are added. After stirring overnight the reaction mixture is diluted with dichloromethane, washed with water and brine and dried over Na2SO4. After filtration the solvent is evaporated and the residue is purified by chromatography (silicagel, eluents: ethylacetate/hexane). The obtained mixture of the two stereoisomers is separated by HPLC (Chiralpak AD-H 5 μm, eluents: hexane/ethanol) yielding 3.7 mg (10.2%) of the title stereoisomer and 24.7 mg (68%) of the stereoisomer N-{(1S)-1-[(S)-(3-fluorophenyl)-{[1-(4-fluorophenyl)-1H-indazole-5-yl]oxy}methyl}-3-methyl-butyl}-2-methoxyacetamide.

출처