BENZYLGLYCOLATE

A suspension 2-hydoxyaceticacid 47 (70percent in H10127] Glycolic acid (7.60 g, 0.10 mol) was dissolved in10 ml of acetonitrile, into which benzyl bromide (13.60 g, 0.08 mol) was added and uniformly stirred. DBU (12.16 g, 0.08 mol) was slowly added dropwise into the reaction liquid at 00 C. Afier that, the reaction liquid was stirred overnight at room temperature. The reaction liquid was poured into ice water, extracted with ethyl acetate, the combined resultant organic phase was washed with 1 M hydrochloric acid solution and saturated salt water successively, dried with anhydrous sodium sulfate and concentrated by rotary evaporation to give the compound as a yellow oil (12.50 g, 94percent).a. Preparation of benzyl glycolate (0150) Glycolic acid (7.60 g, 0.10 mol) was dissolved in 10 ml of acetonitrile, into which benzyl bromide (13.60 g, 0.08 mol) was added and uniformly stirred. DBU (12.16 g, 0.08 mol) was slowly added dropwise into the reaction liquid at 0° C. After that, the reaction liquid was stirred overnight at room temperature. The reaction liquid was poured into the ice water, extracted with ethyl acetate, the combined resultant organic phase was washed with 1M hydrochloric acid solution and saturated salt water successively, dried with anhydrous sodium sulfate and concentrated by rotary evaporation to give the compound as a yellow oil (12.50 g, 94percent).NaH (6.31 g, 158 mmol) was suspended in dry THF (500 ml) and cooled to 0° C. 2-hydroxyacetic acid (12 g, 158 mmol) was added portion wise, and the mixture was stirred at RT for 1 hour. The solvent was removed, and the residue was suspended in DMF (500 ml); KI (2.488 g, 14.99 mmol) and benzyl bromide (18.77 ml, 158 mmol) were added; and the mixture was heated to 100° C. for 24 hours. The solvent was removed, and the crude was portioned between EtOAc (600 ml) and water (200 ml). The organic phase was washed with brine and dried over NaA mixture of 2-hydroxyacetic acid (5.0 g, 65.7 mmol), l, 8-diazabicyclo[5.4.0]undec-7- ene (9.9 g, 65.7 mmol) and benzyl bromide (13.0 g, 78.9.mmol) in toluene (150 mL) was refluxed overnight. The reaction mixture was worked up and the crude product was purified by silica gel flash column chromatography (eluent 20-50percent ethyl acetate in hexane) to give tert- butyl benzyl 2-hydroxyacetate (6.9g, yield 63percent) as a colorless oil. *H NMR (400 MHz, CDC1NaH (6.31 g, 158 mmol) was suspended in dry THF (500 ml) and cooled to 0°C. 2-hydroxyacetic acid (12 g, 158 mmol) was added portion wise and the mixture was stirred at RT for lh. The solvent was removed and the residue was suspended in DMF (500 ml); KI (2.488 g, 14.99 mmol) and benzyl bromide (18.77 ml, 158 mmol) were added and the mixture was heated to 100°C for 24h. The solvent was removed and the crude was portioned between EtOAc (600 ml) and water (200 ml). The organic phase was washed with brine and dried over NaB. B. General procedure: Benzyl alcohol (1.2 equiv) and p-toluenesulfonic acid (0.1 equiv) were taken in benzene and refluxed for 0.5 h, then compounds 10(A-G) (1 equiv) was added, and continuously reflexed until the completion of the reaction (monitored by TLC: petroleum ether/ethyl acetate, 8:1; typically 4 h). The reaction mixture was washed with saturated NaHCO

Benzyl Glycolate was utilized as a potential moiety for the preparation of phosphonate dipeptides as potential inhibitors of VanX.