Sodium Azide → 1-Amino-2-(3,4-difluorophenyl)propan-2-ol

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-(3,4-difluorophenyl)-2-methyl-oxirane (1.2 g, 7.06 mmol) in 10 mL of acetonitrile was added sodium azide (0.69g, 10.6 mmol) followed by lithium perchlorate (1.13 g, 10.6 mmol) and the suspension was heated to reflux overnight. After cooling, it was extracted with EtOAc, washed with saturated NaHCO3, dried over Na2SO4, filtered and the solvent was removed in vacuo. The light bron oil that was obtained was a 10:1 mixture of 1-azido-2-(3,4-difluorophenyl)-propan-2-ol and 2-azido-2-(3,4-difluorophenyl)-propan-1-ol (crude wt 2.0 g). It was dissolved in 40 mL of diethyl ether, cooled to 0° C. and then treated with a solution of lithium aluminum hydride (20.0 mL, 20 mmol). The resulting yellow suspension was then stirred at room temperature for 2 h. The reaction mixture was cooled to 0° C. and then carefully quenched sequentially with 0.8 mL of water, 0.8 mL of 3N NaOH followed by 2.5 mL of water. The resulting suspension was filtered through a fritted glass funnel. To the residue was added 100 mL Et2O and the suspension was heated to reflux for 20 min. The suspension was filtered and was combined with the previous filtrate, dried over MgSO4, filtered and the solvent was removed in vacuo. 1-Amino-2-(3,4-difluorophenyl)-propan-2-ol and 2-amino-2-(3,4-difluorophenyl)-propan-1-ol was obtained as a yellow glassy syrup (1.16 g, 87%) which was used in the next step immediately without further purification.

Provenance & Evidence