Sodium Azide → (1R,5S,6R)-5-(5-amino-2-fluorophenyl)-5-(fluoromethyl)-2-oxa-4-azabicyclo[4.1.0]hept-3-en-3-amine

Participants

Reaction Conditions

Reaction Steps

To a mixture of (1R,5S,6R)-5-(5-bromo-2-fluorophenyl)-5-(fluoromethyl)-2-oxa-4-azabicyclo[4.1.0]hept-3-en-3-amine (6g-B, 0.61 g, 1.9 mmol), sodium azide (0.388 g, 5.96 mmol), (+)-sodium 1-ascorbate (0.080 g, 0.41 mmol), copper(I) iodide (0.086 g, 0.45 mmol) and (1R,2R)-(−)-N,N″-dimethylcyclohexane-1,2-diamine (0.075 mL, 0.47 mmol) under argon atmosphere were added EtOH (2.40 mL) and water (1.2 mL). The reaction mixture was heated at 70° C. for 1.5 h. The cooled reaction mixture was poured into a mixture of 10:1 NH4Cl/ammonium hydroxide and diluted with CH2Cl2. The aqueous layer was extracted with CH2Cl2 (3×) and the combined organic extracts were washed with aqueous saturated NH4Cl solution. The solution was dried over MgSO4 and the filtrate was concentrated in vacuo to give a yellow solid, which was dissolved in THF (8.4 mL) and water (2.8 mL). Trimethylphosphine (1.0 M solution in THF, 1.924 mL, 1.924 mmol) was added and the reaction mixture was stirred at RT for 20 min. The reaction was diluted with CH2Cl2 and water. The phases were separated and the aqueous layer was extracted with CH2Cl2. The combined organic extracts were dried over MgSO4 and the filtrate was purified by silica gel flash column chromatography (0% to 5% 2 M NH3 in MeOH/CH2Cl2) to afford the title compound (0.4473 g, 1.766 mmol, 92% yield) as a maize color solid. MS m/z=254.0 [M+H]+. Calculated for C12H13F2N3O 253.1.

Provenance & Evidence