Sodium Azide → 1-(Azidomethyl)-4-methoxybenzene

Temperature

25 °C

A solution of 4-methoxybenzyl chloride 1000 (51.8 g, 331.0 mmol) in anhydrous DMF (200 mL) was treated with solid sodium azide (21.5 g, 331.0 mmol, 1.0 equiv) at 25° C., and the resulting mixture was stirred at 25° C. for 24 h. When TLC and HPLC/MS showed that the reaction was complete, the reaction mixture was quenched with H2O (400 mL) and ethyl acetate (EtOAc, 400 mL) at room temperature. The two layers were separated, and the aqueous layer was extracted with EtOAc (200 mL). The combined organic extracts were washed with H2O (2×200 mL) and saturated NaCl aqueous solution (100 mL), dried over MgSO4, and concentrated in vacuo. The crude 4-methoxybenzyl azide (51.2 g, 53.95 g theoretical, 94.9% yield) was obtained as colorless oil, which by HPLC and 1H NMR was found to be essentially pure and was directly used in the subsequent reaction without further purifications. For 4-methoxybenzyl azide 1001: 1H NMR (300 MHz, CDCl3) δ 3.84 (s, 3H, ArOCH3), 4.29 (s, 2H, Ar—CH2), 6.96 (d, 2H, J=8.7 Hz), 7.28 (d, 2H, J=7.8 Hz).

1. customthe reaction mixture was quenched with H2O (400 mL) and ethyl acetate (EtOAc, 400 mL) at room temperature
2. customThe two layers were separated
3. extractionthe aqueous layer was extracted with EtOAc (200 mL)
4. washThe combined organic extracts were washed with H2O (2×200 mL) and saturated NaCl aqueous solution (100 mL)
5. dry with materialdried over MgSO4
6. concentrationconcentrated in vacuo

ORD record

ord-facf6ce9f5be4111b8a77d8c38e952c6

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08796465B2