反应详情

To a solution of Intermediate S (5.80 g, 17.7 mmol) in DCM (200 mL) at 0° C. is added acetic acid chlorocarbonylmethyl ester (2.16 mL, 19.5 mmol) followed by DIPEA (7.50 mL, 35.4 mmol) and the mixture stirred at rt for 1 h. The reaction was concentrated and the residue dissolved in 4:1 MeOH/water (100 mL) then treated with LiOH monohydrate (2.23 g, 53.1 mmol). After 72 h, the reaction is poured into ice water and the resulting solid isolated by filtration. The solid is suspended in refluxing tert-butylmethyl ether (400 mL) for 20 min and the remaining undissolved material separated out by filtration. The cooled filtrate produces a solid that is then isolated by filtration in several crops. The undissolved material from the first filtration is dissolved in refluxing 1,4-dioxane and cooled to give an additional crop of solid. The crops are combined to give the title product 253. (LC/MS method 16: ES+ m/z 370.3 [M+H]+, Rt=0.35 min)

1. concentrationThe reaction was concentrated
2. dissolutionthe residue dissolved in 4:1 MeOH/water (100 mL)
3. waitAfter 72 h
4. customthe resulting solid isolated by filtration
5. customthe remaining undissolved material separated out by filtration
6. customThe cooled filtrate produces a solid
7. customthat is then isolated by filtration in several crops
8. filtrationThe undissolved material from the first filtration
9. dissolutionis dissolved
10. temperaturein refluxing 1,4-dioxane
11. temperaturecooled
12. customto give an additional crop of solid