Sodium hydride → HCID 86701731, compound

Participants

Reaction Conditions

Reaction Steps

To a suspension of (±)-2-(2,2,2-trifluoro-1-hydroxy-1-(5-methoxy-7-methyl-1H-indol-4-yl)ethyl)benzo[d]oxazole-5-carbonitrile (Example 128-A) (50 mg, 0.100 mmol) in DMF (0.3 ml), NaH (oil dispersion, 60%) (11.96 mg, 0.299 mmol) was added at rt under nitrogen. After stirring for 15 min., 3-bromo-2,2-dimethylpropionic acid methyl ester (0.043 ml, 0.299 mmol; CAS#30452-00-7) was added at the same temperature. The mixture was warmed up to 90° C. After stirring for 2 h, the mixture was cooled to rt and diluted with EtOAc and 1M NaHSO4aq. The organic layer was separated, dried over Na2SO4, filtered, and concentrated. To a solution of the resulting residue in THF (0.5 ml), potassium trimethylsilanolate (38.5 mg, 0.300 mmol) was added at rt under nitrogen. After stirring for 19 h, additional THF (0.5 ml) and potassium trimethylsilanolate were added. The mixture was heated at 50° C. for 1 h, and then the mixture was cooled to rt. The mixture was diluted with EtOAc, 1M HCl aq. and brine. The layers were separated and the aqueous layer extracted twice with EtOAc. The combined organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated. The crude was purified by RP-HPLC (HC-A) to give the title compound as a 0.25-TFA salt.

Provenance & Evidence