N,N,N',N'-Tetramethylethylenediamine → HCID 19784319, compound

Participants

Reaction Conditions

Reaction Steps

A solution of the compound of Example 20 (3.8 g, 0.1 mmol) and N,N,N',N'-tetramethylethylenediamine (0.75 mL, 5.0 mmol) in dry ether (70 ml) was cooled to 0° C. and treated with a solution of n-BuLi (2.5M) in hexane (8.0 mL, 20 mmol). The mixture was stirred at 0° C. for 0.25 hour and then at room temperature for an additional 3 hours. At this point the mixture was cooled to -78° C. A solution of the compound of Example 5 (1.4 g, 10.0 mmol) in dry THF (15 ml) was then added dropwise and the resulting mixture was stirred at -78° to -60° C. over 1 hour. The reaction was quenched by addition of saturated NH4Cl solution and was allowed to warm to room temperature. The mixture was diluted with ether and H2O. The ether layer was separated and concentrated to leave an oil which was taken up in a mixture of 1N HCl (70 mL) and THF (105 mL). The resulting solution was stirred at room temperature overnight. The mixture was then diluted with H2O and extracted twice with ether. The extracts were set aside for later recovery of unreacted compound of Example 5 while the aqueous layer was made basic by addition of solid NaOH and extracted twice again with ether. These extracts were combined, dried (Na2SO4) and concentrated in vacuo to leave a dark oil. This was placed under high vacuum and warmed to remove 4-fluoro-α-methyl-benzenemethanamine. The crude product was then subjected to flash chromatography on SiO2 using successively CHCl3 and 2% MeOH/CHCl3 as eluants. Fractions containing the title compound were combined and concentrated to afford an oil, 540 mg (21%).

Provenance & Evidence