反应详情

To a stirred solution of [(2R,3R,4S,5R,6R)-3,4,5-triacetoxy-6-[3-[[4-(3-chloropropoxy)phenyl]methyl]-4-methyl-indol-1-yl]tetrahydropyran-2-yl]methyl acetate (143.38 mmoles; 118.40 g) in acetonitrile (829 mL) add 1-[2-(3,8-diazaspiro[5.5]undecan-3-yl)-2-oxo-ethyl]-3-isobutyl-urea (143.38 mmoles; 47.35 g), potassium carbonate (286.75 mmoles; 39.63 g), and potassium iodide (143.38 mmoles; 23.80 g). Heat the mixture at reflux under nitrogen overnight. Cool the reaction mixture to room temperature and add acetic acid anhydride (1.43 moles; 135.53 mL) and N,N-dimethyl-4-pyridinamine (14.34 mmoles; 1.75 g). Stir the mixture for 1 hour. Concentrate the mixture under reduced pressure and partition the residue between water and EtOAc. Separate the organic layer and wash with brine, dry over MgSO4, filter, and concentrate under reduced pressure. The residue is combined with another lot prepared in a similar manner starting from [(2R,3R,4S,5R,6R)-3,4,5-triacetoxy-6-[3-[[4-(3-chloropropoxy)phenyl]methyl]-4-methyl-indol-1-yl]tetrahydropyran-2-yl]methyl acetate (6.2 mmol). Purify by flash column chromatography on silica gel (1.5 kg) eluting with 99:1 EtOAc:triethylamine (1cv), EtOAc (3cv's) and 190:10:1 EtOAc:MeOH:triethylamine (5cv's) to afford the title compound (68.2 g; 49% yield) mass spectrum (m/z): 918.6 (M+1).

1. temperatureHeat the mixture
2. temperatureat reflux under nitrogen overnight
3. concentrationConcentrate the mixture under reduced pressure
4. custompartition the residue between water and EtOAc
5. customSeparate the organic layer
6. washwash with brine
7. dry with materialdry over MgSO4
8. filtrationfilter
9. concentrationconcentrate under reduced pressure
10. customprepared in a similar manner
11. customPurify by flash column chromatography on silica gel (1.5 kg)
12. washeluting with 99:1 EtOAc