Di-tert-butyl Chloromethyl Phosphate

• Di-tert-butyl Chloromethyl Phosphate [D5835]
• 4-Hydroxybenzaldehyde [H0198]
• Sodium Hydride (60%, dispersion in Paraffin Liquid) [S0481]
• Potassium Iodide [P1721]
• DMF

To a solution of 4-hydroxybenzaldehyde (0.25 g, 2.0 mmol) in DMF (5 mL) was added sodium hydride (60%, dispersion in paraffin liquid) (0.12 g, 3.1 mmol) and the mixture was stirred at ambient temperature for 0.5 hour. The suspension was added di-tert-butyl chloromethyl phosphate (0.58 g, 2.3 mmol) and potassium iodide (1.0 g, 6.1 mmol), and stirred for 25 hours. The suspension was poured into water (20 mL) and cooled with an ice bath. Then saturated ammonium chloride aqueous solution (5 mL) was added. The mixture was extracted with diethyl ether and the organic layer was washed with saturated brine, dried over magnesium sulfate, filtered and the filtrate was concentrated under reduced pressure. The given residue was purified by column chromatography (ethyl acetate:hexane = 1:4 - 2:3 on silica gel) to give compound 1 (0.27 g, 38%) as a colorless oil.

The reaction mixture was monitored by TLC (ethyl acetate:hexane = 1:1, Rf = 0.33).

Compound 1

¹H NMR (400 MHz, CDCl₃); δ 9.92 (1H, s), 7.87 (2H, d, J = 8.4 Hz), 7.20 (2H, d, J = 8.4 Hz), 5.70 (2H, d, J = 12.0 Hz), 1.46 (18H, s).

• Synthesis and Characterization of a Phosphate Prodrug of Isoliquiritigenin
• K. Boyapelly, M.-A. Bonin, H. Traboulsi, A. Cloutier, S. C. Phaneuf, D. Fortin, A. M. Cantin, M. V. Richter, E. Marsault, J. Nat. Prod. 2017, 80, 879.