Tetrahydrofuran → HCID 86732209, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of (4S,6S)-4-(3-bromophenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine (0.480 g, 1.352 mmol), sodium azide (0.142 ml, 4.05 mmol), copper(I) iodide (9.16 μl, 11, 0.270 mmol) and L(+)-ascorbic acid sodium salt (0.027 g, 0.135 mmol) was purged with N2 followed by the addition of (1R,2R)-(−)-N,N″-dimethylcyclohexane-1,2-diamine (0.064 ml, 0.405 mmol) and degassed EtOH/water (3/1.5 mL). The resulting mixture was heated at 90° C. for 30 min, then cooled to room temperature, and poured into a mixture of 9:1 saturated NH4Cl solution/NH4OH. The resulting mixture was extracted with EtOAc three times. The combined organic layers were dried over Na2SO4, filtered and concentrated. This product was dissolved in a mixture of THF/water (3/1.5 mL) followed by the addition of trimethylphosphine, 1.0M solution in tetrahydrofuran (1.622 ml, 1.622 mmol) and stirred at room temperature for 30 min. The mixture was worked up with water and extracted with dichloromethane three times. The combined organic layers were dried on sodium sulfate, filtered and concentrated. The crude material was purified by column chromatography using 5-10% MeOH/dichloromethane to give (4S,6S)-4-(3-aminophenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine (0.322 g, 82% yield). MS m/z=292.0 [M+H]+. Calculated for C12H13F4N3O: 291.2

Provenance & Evidence