반응 #520322

반응 방정식

[(2R)-8-methoxy-3,4-dihydro-2H-chromen-2-yl]methyl 4-methylbenzenesulfonate

6-fluoro-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole

→

6-fluoro-3-(1-{[(2R)-8-methoxy-3,4-dihydro-2H-chromen-2-yl]methyl}-1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole

수율 62.0%

용매

ethyl acetate

methyl sulfoxide

반응 조건

후처리

1. 1
   온도to cool to room temperature
2. 2
   세척washed with water (2×100 mL), aqueous sodium chloride (100 mL)
3. 3
   건조dried (magnesium sulfate)
4. 4
   기타the solvent was removed in vacuo
5. 5
   기타to give a crude solid
6. 6
   기타Purification by flash column chromatography (silica, ethyl acetate:hexanes 4:1)
7. 7
   기타followed by recrystallization from ethanol

실험 절차

To a solution of [(2R)-8-methoxy-3,4-dihydro-2H-chromen-2-yl]methyl 4-methylbenzenesulfonate (0.348 g, 1.00 mmol) in methyl sulfoxide (20 mL) was added 6-fluoro-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole (0.865 g, 4.00 mmol) and the reaction mixture was heated to 80° C. for 12 h. The reaction mixture was allowed to cool to room temperature and was diluted with ethyl acetate (200 mL), washed with water (2×100 mL), aqueous sodium chloride (100 mL), dried (magnesium sulfate) and the solvent was removed in vacuo to give a crude solid. Purification by flash column chromatography (silica, ethyl acetate:hexanes 4:1) followed by recrystallization from ethanol provided 0.243 g (62%, 40% ee) of 6-fluoro-3-(1-{[(2R)-8-methoxy-3,4-dihydro-2H-chromen-2-yl]methyl}-1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole as a tan crystalline powder. [α]D25=−27.14 (c 9.95 in chloroform, 40% ee); Rf=0.47 (silica, ethyl acetate:hexanes 4:1); mp >170° C. dec; Anal. Calcd. for C24H25FN2O2.0.1 H2O: C, 73.11; H, 6.44; N, 7.11. Found: C, 72.81; H, 6.36; N, 7.06.

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