Trichloroacetonitrile → HCID 23643784, compound

Participants

Reaction Steps

A solution of 3-pentanol (1 mmol) in anhydrous Et2O (0.2 mL) was added dropwise to NaH (0.1 mmol; 60% in mineral oil) suspended in Et2O (1 mL) under nitrogen. The mixture was stirred for 10 min at room temperature and then added dropwise over a period of 20 min to a solution of trichloroacetonitrile (1.5 mmol) in Et2O (1 mL) at −5° C. under nitrogen. The reaction mixture was warmed to room temperature, and stirred for 2 h. After removal of solvent, the residue was triturated with MeOH/hexane with vigorous stirring to give precipitates, which were filtered off and washed with cold hexane. The filtrate was evaporated under reduced pressure to give 3-pentyl trichloroacetimidate. The freshly prepared 3-pentyl trichloroacetimidate (0.75 mmol) and CF3SO3H (0.075 mmol) were added to a solution of azido carboxylate ester (2A) (0.6 mmol) in CH2Cl2 (5 mL) under nitrogen. The reaction mixture was stirred at room temperature for 24 h, during which more imidate and CF3SO3H (0.075 mmol) were added 5 times every 4 h period. The reaction was quenched with 5% aqueous NaHCO3 solution. The aqueous layer was extracted with CH2Cl2 (2×). The combined organic phase was washed with brine, dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash column chromatography (EtOAc/hexane) to afford the product (14B). Azide (14B) can then be converted to amine (1) as described above.

Provenance & Evidence