反应详情

温度

88 °C

A mixture of methyl 5-bromo-3-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-2-methylbenzoate (580 g, 1.63 mol), 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)morpholine (592 g, 1.95 mol), 1,4-dioxane (3.86 L), sodium carbonate (618 g, 5.83 mol), and water (771 ml) was degassed by bubbling nitrogen through the mixture at 20° C. for 20 minutes and treated with tetrakis(triphenylphosphine)palladium(0) (14.11 g, 12.21 mmol). The resulting mixture was degassed for an additional 20 minutes and then heated to 87-89° C. for 17 h. After cooling to 20° C., the mixture was diluted with ethyl acetate (5.80 L) and a solution of (R)-2-Amino-3-mercaptopropionic acid (232 g) in water (2.320 L). After stirring for 1 h at 20° C., the organic layer was separated and washed again with a solution of (R)-2-Amino-3-mercaptopropionic acid (232 g) in water (2.320 L). The aqueous layers were combined and extracted with ethyl acetate (5.80 L). The organic layers were combined, washed with a solution of sodium hydroxide (93 g) in water (2.32 L), and concentrated under vacuum at 35° C. to give the title compound as an orange oil (1.21 kg, 164% yield).

1. customwas degassed
2. customby bubbling nitrogen through the mixture at 20° C. for 20 minutes
3. customThe resulting mixture was degassed for an additional 20 minutes
4. temperatureAfter cooling to 20° C.
5. additionthe mixture was diluted with ethyl acetate (5.80 L)
6. customthe organic layer was separated
7. washwashed again with a solution of (R)-2-Amino-3-mercaptopropionic acid (232 g) in water (2.320 L)
8. extractionextracted with ethyl acetate (5.80 L)
9. washwashed with a solution of sodium hydroxide (93 g) in water (2.32 L)
10. concentrationconcentrated under vacuum at 35° C.