2,6-Dimethoxyphenol → Ethyl (2,6-dimethoxyphenoxy)acetate

Participants

Reaction Conditions

Reaction Steps

To a solution of 2,6-dimethoxyphenol (1.54 g, 10 mmol) and ethyl bromoacetate (2.00 g, 12 mmol) in 15 mL of anhydrous DMF, was added 2.76 g (20 mmol) of K2CO3. The reaction mixture was stirred at 30° C. for 20 hours. The mixture was concentrated in vacuo to remove volatiles. The resulting residue was extracted with EtOAc, washed with brine, dried over anhydrous sodium sulfate and then concentrated in vacou to give 2.2 g (91.6%) of ethyl 2-(2,6-dimethoxyphenoxy)acetate. The obtained ester (1.2 g, 5 mmol) was dissolved in a suspension of Silica Gel (2.0 g) in 20 mL of DCM. To this was dropwise added of a solution of concentrated HNO3 (20 mL) in 20 mL of DCM at rt. After being stirred at room temperature for 1 hour, it was transferred into a separatory funnel and then brown bottom layer was discarded into 100 g of ice. The remaining top organic layer was washed with brine, dried over anhydrous sodium sulfate, and then concentrated in vacou to give 1.4 g (98%) of ethyl 2-(2,6-dimethoxy-4-nitrophenoxy)acetate as a brown solid. The obtained nitrophenoxy ester (1.34 g, 4.7 mmol) was dissolved in anhydrous THF (20 mL). To this, was slowly added of 1M DIBAL solution (10.3 mL, 10.3 mmol) in toluene with ice bath cooling. After 1 hour at rt, the reaction was quenched by addition of 1N-NaOH solution, and then extracted with EtOAc. The obtained organic layer was dried over anhydrous sodium sulfate, and passed through Silica Gel pad. The resulting filtrate was concentrated in vacuo to afford 2-(2,6-dimethoxy-4-nitrophenoxy)ethanol (1.01 g, 88%) as a pale yellow solid; MS (ESI) m/z 326 [M+H]+.

Provenance & Evidence