Step 1: Synthesis of dibenzyl chloromethyl phosphate (33B)
Dibenzyl chloromethyl phosphate (33A) (5.0 g, 0.018 mol) was dissolved in a solvent mixture of dichloromethane (50 mL) and water (50 mL), followed by the addition of tetrabutylammonium sulfate (1.22 g, 0.0036 mol) as a phase transfer catalyst. Sodium bicarbonate (6.0 g, 0.072 mol) was slowly added to adjust the pH of the reaction system under cooling conditions in an ice-water bath. Next, chloromethanesulfonyl chloride (2.97 g, 1.9 mL) was added dropwise to the reaction mixture. The reaction mixture was stirred at room temperature overnight. Upon completion of the reaction, the reaction was allowed to partition, the organic phase was separated, and the aqueous phase was extracted with dichloromethane (50 mL). The organic extracts were combined and washed with saturated sodium chloride solution (100 mL x 2) to remove residual water-soluble impurities. The organic layers were dried over anhydrous sodium sulfate and concentrated under reduced pressure to remove the solvent. The crude product was purified by silica gel column chromatography using a gradient elution of petroleum ether/ethyl acetate (v/v = 5:1→3:1) to afford dibenzyl chloromethyl phosphate (33B) as a colorless liquid (4.35 g, yield: 74.1%).
1H NMR (400 MHz, CDCl3): δ 7.36-7.26 (m, 10H), 5.63 (d, 2H), 5.10 (d, 4H).
