反应详情

温度

2 °C

(4R)-5,5-Dimethyl-thiazolidine-3,4-dicarboxylic acid 3-tert-butyl ester (which can be prepared according to the methods of Ikunaka, M. et al., Tetrahedron Asymm. 2002, 13, 1201; Mimoto, T. et al., J. Med. Chem. 1999, 42, 1789; and Mimoto, T. et al., European Patent Application 0574135A1 (1993), 250 g; 0.957 mol) was added to an argon-purged 5-L flask and was dissolved in EtOAc (1.25 L). The solution was cooled to 2° C. and (PhO)2POCl (208 mL; 1.00 mol) was then added in one portion. NEt3 (280 mL; 2.01 mol) was added dropwise via addition funnel and the resulting suspension was then stirred at 0° C. Seven minutes later, allylamine (75.4 mL; 1.00 mol) was added dropwise. The ice bath was removed and the suspension was allowed to warm to room temperature. One-half hour later, 1 N HCl (750 mL; 0.750 mol) was added. The mixture was transferred to a 4-L separatory funnel using EtOAc (50 mL) for rinsing. The layers were separated. The organic fraction was washed with 7.2% aqueous Na2CO3 (2×1.25 L), and was then transferred to a 3-L distillation flask and was diluted with EtOAc (400 mL). The solution was dried azeotropically and concentrated to a volume of 800 mL by distillation of EtOAc at one atmosphere. After cooling to 25° C., the resulting clear yellowish EtOAc solution of (4R)-4-allylcarbamoyl-5,5-dimethyl-thiazolidine-3-carboxylic acid tert-butyl ester was carried on directly into the next step. An aliquot was removed and concentrated to give (4R)-4-allylcarbamoyl-5,5-dimethyl-thiazolidine-3-carboxylic acid tert-butyl ester as a white crystalline solid: mp=94–98° C., 1H NMR (300 MHz, CDCl3) δ 6.12 (br s, 1H), 5.88 (app ddt, J=10.2, 17.1, 5.6 Hz, 1H), 5.28 (app dq, J=17.1, 1.5 Hz, 1H), 5.18 (app dd, J=1.2, 10.2 Hz, 1H), 4.68 (s, 2H), 4.14 (br s, 1H), 3.95 (br t, J=5.4 Hz, 2H), 1.62 (s, 3H), 1.49 (s, 9H), 1.46 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 170.0, 154.0, 134.4, 116.9, 82.0, 73.3, 54.0, 48.7, 42.0, 30.6, 28.6, 24.6; MS (CI) m/z 301.1599 (301.1586 calcd for C14H25N2O3S, M+H+); elemental analysis calcd for C14H24N2O3S: C, 55.97; H, 8.05; N, 9.32; found: C, 56.11; H, 8.01; N, 9.11.

1. addition0.957 mol) was added to an argon-
2. custompurged 5-L flask
3. dissolutionwas dissolved in EtOAc (1.25 L)
4. customThe ice bath was removed
5. temperatureto warm to room temperature
6. customThe mixture was transferred to a 4-L separatory funnel
7. washfor rinsing
8. customThe layers were separated
9. washThe organic fraction was washed with 7.2% aqueous Na2CO3 (2×1.25 L)
10. distillationwas then transferred to a 3-L distillation flask
11. additionwas diluted with EtOAc (400 mL)
12. customThe solution was dried azeotropically
13. concentrationconcentrated to a volume of 800 mL by distillation of EtOAc at one atmosphere
14. temperatureAfter cooling to 25° C.
15. customAn aliquot was removed
16. concentrationconcentrated