反应详情

12 ml (6.0 mmol) of potassium hexamethyldisilylamide (0.5 M solution in toluene) at −20° C. under nitrogen is added, dropwise, to the solution of 2.0 g (5.64 mmol) of methyl 2-amino-5-[(8-hydroxy-1-methoxy-2-methyl-indolizin-3-yl)carbonyl]benzoate (described in stage F of Example 1) in 56 ml of tetrahydrofuran. The formation of a red precipitate is observed. The mixture is allowed to return to ambient temperature and 18.5 g (33.9 mmol) of 1,20-diiodo-3,6,9,12,15,18-hexaoxaicosane are added (Example R1). The solution is stirred at ambient temperature for 18 hours. The reaction medium is poured into a solution of hydrochloric acid (1 M) and the mixture is extracted with an ethyl acetate/tetrahydrofuran mixture. The organic phase is washed with a saturated aqueous solution of sodium chloride, dried over sodium sulphate and concentrated under reduced pressure. The residue obtained is purified by flash chromatography on silica gel (gradient of dichloromethane/methanol: 100/0 to 90/10). 2.3 g (53%) of a yellow oil are obtained.

1. customto return to ambient temperature
2. extractionthe mixture is extracted with an ethyl acetate/tetrahydrofuran mixture
3. washThe organic phase is washed with a saturated aqueous solution of sodium chloride
4. dry with materialdried over sodium sulphate
5. concentrationconcentrated under reduced pressure
6. customThe residue obtained
7. customis purified by flash chromatography on silica gel (gradient of dichloromethane/methanol: 100/0 to 90/10)