反应详情

5.4 ml (9.31 mmol) of potassium hexamethyldisilylamide (0.5 M solution in toluene) and then 0.69 ml (4.66 mmol) of tert-butyl 2-bromoacetate are added, dropwise, to the solution of 1.50 g (4.23 mmol) of methyl 2-amino-5-[(8-hydroxy-1-methoxy-2-methylindolizin-3-yl)carbonyl]benzoate (Stage F of Example 1) in 15 ml of tetrahydrofuran at −20° C. under argon. The mixture is stirred for 2 hours, allowing it to return to ambient temperature. The reaction medium is poured into a saturated aqueous solution of potassium hydrogen sulphate and the mixture is extracted with ethyl acetate. The organic phase is washed with a saturated aqueous solution of sodium chloride, dried over sodium sulphate, and concentrated under reduced pressure. The oil obtained is purified by flash chromatography on silica gel (dichloromethane/methanol gradient=100/0 to 90/10). 1.26 g (64%) of a yellow powder are obtained.

1. customat −20° C.
2. customto return to ambient temperature
3. extractionthe mixture is extracted with ethyl acetate
4. washThe organic phase is washed with a saturated aqueous solution of sodium chloride
5. dry with materialdried over sodium sulphate
6. concentrationconcentrated under reduced pressure
7. customThe oil obtained
8. customis purified by flash chromatography on silica gel (dichloromethane/methanol gradient=100/0 to 90/10)