N,N,N',N'-Tetramethylethylenediamine → tert-butyl 2-((6-(3,5-dimethylisoxazol-4-yl)-2-ethoxy-1H-benzo[d]imidazol-4-yl)(hydroxy)methyl)pyrrolidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

N-Boc-pyrrolidine (150 mg, 0.39 mmol) and TMEDA (0.2 mL, 158 mg, 1.36 mmol) was dissolved in dry MeTHF (2.6 mL) under Ar and cooled to −78° C. Sec-BuLi (1.4M, 0.97 mL, 1.36 mmol) was added dropwise and the reaction was allowed to stir at −78° C. for 40 mins. tert-butyl 6-(3,5-dimethylisoxazol-4-yl)-2-ethoxy-4-formyl-1H-benzo[d]imidazole-1-carboxylate (150 mg, 0.39 mmol) was dissolved in MeTHF (0.5 mL) and added dropwise via syringe to the reaction and allowed to stir at −78° C. for 10 minutes. The reaction was quenched with water and extracted three times with EtOAc, combined organic layers were washed once with brine, concentrated, and purified by reverse-phase HPLC to give tert-butyl 2-((6-(3,5-dimethylisoxazol-4-yl)-2-ethoxy-1H-benzo[d]imidazol-4-yl)(hydroxy)methyl)pyrrolidine-1-carboxylate (53 mg, 30%) as a white powder. The solid (50 mg, 0.11 mmol) was dissolved in EtOH (5 mL) and HCl (1 mL) and heated for 12 hours at 65° C. The reaction was cooled and concentrated to afford the desired product as a white powder.

Provenance & Evidence