反应详情

温度

87.5 °C

To a solution of K2CO3 (526.2 mg, 3.80 mmol) in water (1.6 mL, 6 volume) was added isovaline-HCl (292.4 mg, 1.90 mmol). The resulting solution was stirred for 10 minutes. A solution of [14C] enriched 2,4-dichloropyrimidine (11a**) (0.261 g, 90 mCi) in isopropanol (5.2 mL, 20 volume) was added dropwise at room temperature, and the resulting mixture was heated at 85-90° C. for 18 hours. The mixture was then concentrated to 4 volumes, then 1N NaOH (6 mL) and isopropyl acetate (6 mL) were added. The aqueous phase was separated and the organic phase was extracted with 1N NaOH (6 mL×2). The combined aqueous layer was acidified to pH=3.0-3.5 using 6N HCl (aq). The resulting solution was extracted with isopropyl acetate (15 mL×3). The collected organic layer was concentrated to 3-4 volumes, then 1N HCl etherate (1.73 mL, 1.73 mmol) was added drop wise at 0° C. and stirred for 15 minutes. The organic solvent was decanted and the solid was washed with isopropyl acetate (5 mL×2). The solid was dried under vacuum and obtained 360 mg of (R)-2-(2-chloropyrimidin-4-ylamino)-2-methylbutanoic acid (2a**) with 70% radiochemical purity by instant imager to provide (R)-2-(2-chloropyrimidin-4-ylamino)-2-methylbutanoic acid (2a**).

1. concentrationThe mixture was then concentrated to 4 volumes
2. addition1N NaOH (6 mL) and isopropyl acetate (6 mL) were added
3. customThe aqueous phase was separated
4. extractionthe organic phase was extracted with 1N NaOH (6 mL×2)
5. extractionThe resulting solution was extracted with isopropyl acetate (15 mL×3)
6. concentrationThe collected organic layer was concentrated to 3-4 volumes
7. stirringstirred for 15 minutes
8. customThe organic solvent was decanted
9. washthe solid was washed with isopropyl acetate (5 mL×2)
10. customThe solid was dried under vacuum