Phenethylamine → Thiazole derivative, 29c

Participants

Reaction Conditions

Reaction Steps

To a solution (0.2 M) of 1,3-thiazole-5-carboxylic acid (from Combi-blocks) in dry THF a solution of BuLi (1.6 M solution in hexane, 2.2 eq.) was added dropwise at −78° C. and stirred at −78° C. for 45 min. A solution (1 M) of N-methyl-N-methoxytrifluoroacetamide (1.5 eq.) in dry THF was added at −78° C. to the reaction mixture and stirred for 1 h at −60° C. The reaction mixture was quenched by adding NH4Cl solution, then extracted with DCM. The combined organic layer was washed with brine and dried. Evaporation of the solvent gave a residue (LC-MS (ES+) C6H2F3NO3S requires: 225, found: 226 (M+H)+. Retention time: 2.26 min) that was dissolved in DMF. To the resulting solution (0.5 M), HOBt (1.5 eq.) and EDCI (1.5 eq.) were added and stirring was continued for 1 h. N-benzylmethylamine (1.5 eq.) was added and the reaction mixture was stirred at RT O/N. The crude was purified by RP-HPLC to yield (3%) the title compound as a solid.

Provenance & Evidence