1-Methylimidazole → n-Benzoyl-2-(4-methoxyphenyl)thiazolidine-4-carboxylic acid

Participants

Reaction Steps

Commercially available Fmoc-Cys(Trt) was attached to the linker based solid support # by DIC/DMAP procedure. The solid support (0.50 g) having substitution 0.34 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) (0.56 g, 1.0 mmol) dimethylaminopyridine (DMAP) or N-methyl imidazole (NMI) (0.25 mmol) in DCM:DMF (1:1) 20 ml were added. This mixture was stirred for 8-10 hrs. An aliquot of 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 indicating approximately 88% loading [Method A]. The resin bearing Fmoc-Cys(Trt) was treated 20% piperidine in DCM:DMF (1:1) 12 ml for 20 min to remove Fmoc group. The resin was washed three times with DCM and then treated with 10% trifluroacetic 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) 10 ml was added under stirring. The stirring was continued for 8-10 hrs. The resin was washed three times with DCM. To this resin, a solution of Benzoyl chloride (0.2 ml, 2 mmol) and DIEA (0.4 ml, 2.0 mmol) in DCM:DMF (1:1) 10 ml were added and the stirring was continued for 3 hrs until the resin was negative to Kaiser test. The resin was washed with DCM:DMF (1:1) 10 ml×3, with DMF 10 ml×3, DCM:DMF (1:1) 10 ml×2 and finally 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 N-Benzoyl-2-(4-methoxyphenyl)thiazolidine-4-carboxylic acid as white crystalline material. Yield: 0.043 g, 72%; m.p. 108-110° C.; FAB-MS [M+H]+ 344; 1H NMR (DMSO-d6) δ: 3.3 (m, 2H), 3.9 (s, 3H), 4.7 (bs, 1H), 5.7 (bs, 1H), 6.6 (m 5H), 6.9-7.2 (Abq, 4H).

Provenance & Evidence