Ethanamine, 2,2,2-trifluoro- → (R)-6-((2,2,2-Trifluoroethylamino)methyl)-1,2,3,4-tetrahydronaphthalen-1-amine

Participants

Reaction Conditions

Reaction Steps

A mixture of (R)-(5-(tert-butoxycarbonylamino)-5,6,7,8-tetrahydronaphthalen-2-yl)methyl methanesulfonate (400 mg, 1.13 mmol, 1.0 eq.), 2,2,2-trifluoroethanamine (360 μl, 4.52 mmol, 4.0 eq.) and K2CO3 (470 mg, 3.39 mmol, 3.0 eq.) in THF (10 ml) was heated at 100° C. in sealed tube for 16 h. After completion of the reaction (monitored by TLC), the mixture was diluted with ethyl acetate (50 ml), washed with water (20 ml) and brine (20 ml), and dried over Na2SO4. The solvent was evaporated under reduced pressure to give the crude product which was purified by column chromatography (silica gel; 20% ethyl acetate/hexanes) to yield the title compound as an off-white solid. Yield: 37% (150 mg, 0.412 mmol) 2. (R)-6-((2,2,2-Trifluoroethylamino)methyl)-1,2,3,4-tetrahydronaphthalen-1-amine TFA (1 ml) was added to a solution of (R)-tert-butyl 6-((2,2,2-trifluoroethylamino)-methyl)-1,2,3,4-tetrahydronaphthalen-1-ylcarbamate (230 mg, 0.64 mmol, 1.0 eq.) in DCM (4 ml) at 0° C. and the resulting reaction mixture was stirred at RT for 2 h. The solvent was evaporated under reduced pressure and the residue was azeotroped with toluene to yield the desired product which was used in the next step.

Provenance & Evidence