反应详情

To a solution of methyl 2(R)-[[4-methoxybenzenesulfonyl]amino]-3-methylbutanoate (1662 g, 5.52 mol) in dimethylformamide (10.9 L) is added 3-picolyl chloride hydrochloride (947.3 g, 5.77 mol) followed by powdered potassium carbonate (2409.9 g, 17.36 mol). The reaction mixture is stirred at room temperature for 2 days. At that time, additional quantities of 3-picolyl chloride hydrochloride (95 g) and powdered potassium carbonate (241 g) are added, and the reaction is stirred for 3 more days. The solids are then filtered away, the crude product is poured into water (22 L), and the pH is adjusted to pH=8 with 6N sodium hydroxide. This solution is extracted well with toluene (4×10 L), the combined organic layers are washed with water (2×12 L), and then with 6N hydrochloric acid (3×1600 mL). This aqueous layer is then re-adjusted to pH=8 with 6N sodium hydroxide, extracted with toluene (4×10 L), dried (Na2SO4), and the solvent is evaporated. The oil obtained is re-dissolved in ethyl acetate (12 L), cooled to 5° C., and to this is added methanolic HCl (834 mL). After stirring for 2 hours, the precipitated product is collected by filtration to give methyl 2(R)-[[4-methoxybenzenesulfonyl](3-picolyl)amino]-3-methylbutanoate hydrochloride.

1. stirringthe reaction is stirred for 3 more days
2. filtrationThe solids are then filtered away
3. additionthe crude product is poured into water (22 L)
4. extractionThis solution is extracted well with toluene (4×10 L)
5. washthe combined organic layers are washed with water (2×12 L)
6. extractionre-adjusted to pH=8 with 6N sodium hydroxide, extracted with toluene (4×10 L)
7. dry with materialdried (Na2SO4)
8. customthe solvent is evaporated
9. customThe oil obtained
10. temperaturecooled to 5° C.
11. stirringAfter stirring for 2 hours
12. filtrationthe precipitated product is collected by filtration