反应详情

Commercially available Fmoc-Cys(Trt) was attached to the linker based solid support 1 by DIC/DMAP procedure. The solid support (1.0 g) having substitution 0.4 meq/g was placed in reaction vessel and allowed to swell in dichloromethane (DCM) under nitrogen stirring. After 30 min. the resin was filtered and washed with DCM. To this resin a solution of Fmoc-Cys(Trt) (0.70 g, 1.2 mmol) dimethylaminopyridine (DMAP) or N-methyl imidazole (NMI) (0.4 mmol) in DCM:DMF (1:1) 20 ml and was added. This mixture was stirred for 8-10 hrs. The resin was washed three times with DCM and dried. An aliquot of this resin was tested to check the loading by the treatment with 20% piperidine and subsequently recording the absorbance in UV [Method A]. It came out to be 90% loading. The resin bearing Fmoc-Cys(Trt) was treated with 20% piperidine in DCM:DMF (1:1) 20 ml for 20 min to remove Fmoc group. The resin was washed three times with DCM and then treated with 10% trifluoric acid (TFA)/Bu3SiH in DCM for 30 min (three times) to remove the trityl group of Cys. After washing the resin with DCM 3 times, a solution of p-anisaldehyde (0.5 ml) in DCM:DMF (1:1) 15 ml was added under stirring and the stirring was continued for 8-10 hrs. The resin was washed three times with DCM and dried. It was treated with a mixture of dioxan-MeOH-4N. NaOH (30:9:1, 20 ml) for 30 min under stirring and the resin was filtered and washed with 2 ml of water. The combined filtrate was evaporated in vacuo. The residue was taken in water and extracted with ether. The aqueous layer acidified with 1N hydrochloric acid and extracted with EtOAc (3×70 ml). The combined EtOAc layer was washed with water and brine then dried over Na2SO4 and evaporated in vacuo to yield 2-(4-methoxyphenyl) thiazolidine-4-carboxylic acid as white crystalline material. Yield: 0.061 g, 72%; m.p. 150-51° C.; FAB-MS [M+H]+ 239; 1H NMR (DMSO-d6) δ: 3.5 (m, 2H), 3.7 (s, 3H), 4.8 (bs, 1H), 5.9 (bs, 1H), 6.8-7.1 (Abq, 4H).

1. customwas placed in reaction vessel
2. filtrationAfter 30 min. the resin was filtered
3. washwashed with DCM
4. washThe resin was washed three times with DCM
5. customdried
6. additionwas treated with 20% piperidine in DCM:DMF (1:1) 20 ml for 20 min
7. customto remove Fmoc group
8. washThe resin was washed three times with DCM
9. additiontreated with 10% trifluoric acid (TFA)/Bu3SiH in DCM for 30 min (three times)
10. customto remove the trityl group of Cys
11. washAfter washing the resin with DCM 3 times
12. additiona solution of p-anisaldehyde (0.5 ml) in DCM:DMF (1:1) 15 ml was added
13. stirringunder stirring
14. waitthe stirring was continued for 8-10 hrs
15. washThe resin was washed three times with DCM
16. customdried
17. additionIt was treated with a mixture of dioxan-MeOH-4N
18. stirringNaOH (30:9:1, 20 ml) for 30 min under stirring
19. filtrationthe resin was filtered
20. washwashed with 2 ml of water
21. customThe combined filtrate was evaporated in vacuo
22. extractionextracted with ether
23. extractionextracted with EtOAc (3×70 ml)
24. washThe combined EtOAc layer was washed with water and brine
25. dry with materialthen dried over Na2SO4
26. customevaporated in vacuo