反应详情

温度

0 °C

To a solution of R-(-)-mandelic acid (22.1 g, 0.14 mole) and 1-hydroxy-benzotriazole hydrate (19.6 g, 0.14 mole) cooled to 0° C. was added successively N-methylmorpholine (16.2 g, 0.16 mole), 4-amino-6-cyano-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran (29.4g, 0.14 mole, from Example 8, part D) and 1-(3-dimethylaminopropyl)-2-ethylcarbodiimide.HCl (27.9 g, 0.14 mole). The reaction mixture was stirred 0.5 hours at 0° C. and two hours at room temperature. The solvent was recovered under vacuum and the residue was partitioned between 5% aqueous HCl and ethyl acetate. The organic fraction was washed with saturated sodium bicarbonate solution, saturated sodium chloride solution, dried over magnesium sulfate and evaporated in vacuo to obtain 52 g of yellow gum. The crude diastereomer mixture was chromatographed on silica eluting with 1:1 hexane/ethyl acetate to obtain 19.8 g (40.6%) of Isomer B (isomer A being subject of Example 19, part A); m.p.=135-136° C., [α]D25 =-60.8°. 1H NMR (CDCl3) δ 7.51-7.30 (m, 6H), 7.27 (d, J=1.76 Hz, 1H), 6.80 (m, 2H), 5.18 (m, 1H), 5.08 (d, J=2.93 Hz, 1H), 3.97 (d, J=2.93 Hz, 1H), 2.12 (dd, J=6.15 and 13.19 Hz, 1H), 1.69 (dd, J=11.43 and 13.20 Hz, 1H), 1.40 (s, 3H), 1.30 (s, 3H); 13C NMR (CDCl3) δ 172.59, 157.53, 139.13, 133.07, 132.81, 131.98, 128.92, 126.38, 122.86, 118.97, 118.56, 103.25, 76.83, 74.26, 41.81, 38.96, 29.15, 24.62; MS: (M+H)+ @337.

1. customThe solvent was recovered under vacuum
2. customthe residue was partitioned between 5% aqueous HCl and ethyl acetate
3. washThe organic fraction was washed with saturated sodium bicarbonate solution, saturated sodium chloride solution
4. dry with materialdried over magnesium sulfate
5. customevaporated in vacuo