1-Methylimidazole → 2-(4-Methoxy-phenyl)-thiazolidine-4-carboxylic acid

Beteiligte Stoffe

Reaktionsschritte

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).

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