Ethylenediamine → 2-[4-(4,5-Dihydro-1H-imidazol-2-yl)phenyl]ethan-1-amine

Participants

Reaction Conditions

Reaction Steps

Boc2O (818 mg, 3.75 mmol, 1.5 eq.) was added to a stirred solution of 2-(4-bromophenyl)ethanamine (500 mg, 2.5 mmol, 1.0 eq.) and TEA (1.5 ml, 7.5 mmol, 3.0 eq.) in DCM (25 ml) at 0° C. and resulting reaction mixture is stirred at 25° C. for 6 h. The reaction mixture was diluted with DCM (75 ml), washed with water (2×50 ml) and brine (50 ml) and dried over Na2SO4. The solvent was evaporated under reduced pressure and the residue triturated with hexanes to yield the desired product as an off white solid. Yield: 100% (750 mg, 2.5 mmol) 2. A mixture of tert-butyl 4-bromophenethylcarbamate (750 mg, 2.5 mmol, 1.0 eq.) and Zn(CN)2 (439 mg, 3.75 mmol, 1.5 eq.) in dry DMF (15 ml) was degassed with argon for 15 min. Xanthphos (290 mg, 0.5 mmol, 0.2 eq.) and Pd2(dba)3 (229 mg, 0.25 mmol, 0.1 eq.) were added to the reaction mixture and it was heated to 100° C. for 18 h. The reaction mixture was diluted with water (40 ml) and extracted with ethyl acetate (2×50 ml). The organic layer was washed with brine (50 ml) and dried over Na2SO4. The solvent was evaporated under reduced pressure and the crude product was purified by column chromatography (neutral alumina, 10% ethyl acetate in hexanes) to yield the desired product as a reddish solid. Yield: 73% (450 mg, 1.83 mmol) 3. P2S5 (48 mg) was added to a mixture of tert-butyl 4-cyanophenethylcarbamate (450 mg, 1.83 mmol, 1.0 eq.) and freshly distilled ethylenediamine (2.4 ml, 33.85 mmol, 18.5 eq.) and the resulting reaction mixture was heated to 120° C. for 4 h. The reaction mixture was cooled to 25° C. and poured into ice-cold water (20 ml). It was then extracted with DCM (40 ml). The organic layer was dried over Na2SO4 and the solvent was evaporated under reduced pressure to yield the desired product. Yield: 94% (500 mg, 1.73 mmol) 4. TFA (1 ml) was added to a solution of tert-butyl 4-(4,5-dihydro-1H-imidazol-2-yl)phenethylcarbamate (214 mg, 0.74 mmol, 1.0 eq.) in DCM (3 ml) at 0° C. and the resulting reaction mixture was stirred at RT for 2 h. The reaction mixture was concentrated under reduced pressure to give the crude product which was directly used in the next step.

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