Sodium Iodide → Diethyl (1,1-difluoro-3-(2-(4-formyl-3-methoxyphenoxy)ethoxy)propyl)phosphonate

Participants

Reaction Conditions

Reaction Steps

To a solution of 4-hydroxy-2-methoxybenzaldehyde (1 equiv.) in DMF (0.25 M) was added cesium carbonate (2 equiv.), sodium iodide (0.20 equiv.) and diethyl (3-(2-bromoethoxy)-1,1-difluoropropyl)phosphonate (1.2 equiv.) (described in ref. 88, Ex 7 Step 1). The reaction mixture was stirred at 100° C. for 3 h, after which it was allowed to cool to room temperature. The resulting mixture was then diluted with water and EtOAc. This mixture was transferred to a separatory funnel and washed with water three times. The organic layer was then separated, dried over anhydrous Na2SO4 and the volatiles were removed in vacuo. The resulting residue was purified by a COMBIFLASH™ system using a gradient of 0-5% MeOH/DCM to provide the title compound (79%) as a solid.

Provenance & Evidence