Boc-D-Glutamic acid 5-benzyl ester

A solution of the compound 2 (6.0 g, 25.3mmol), added with Di-tert-butyldicarbonate (Boc2O for an amount of 6.62 g, 30.36 mmol) in dixoane and water(1 :1 , 40 mL) at 0 °C and the mixture was stirred overnight (16 hours). The solvent was removed under reduced pressure and the residue was diluted with water (30 mL), basified with Sodium Carbonate (Na2CO3) and washed with Ethyl Acetate (EtOAc) (3 x 100 mL). The aqueous layer was adjusted to pH 2-3 with a5 M aqueous HCI solution and extracted with EtOAc (4 x 100 mL). The combined organic extracts were washed with brine, dried over Na2504 and the solvent was removed under reduced pressure to get (R)-5-(benzyloxy)-2-(tert-butoxycarbonyl)-5-oxopentanoic acid [Compound 3j (8.19 g, 96percent) as a viscous colourless oil with the following NMR characteristics.1H NMR(CDC13): 7.38-7.31(m, 5H), 5.13 (s, 1H), 2.61-2.41 (m, 2H), 2.23-1.99(m, 2H), 1.43 (s, 9H). ESI MS:36.6 g (1.0eq) H-D-Glu(OBzl)-OH was dissolved in 500 mL dioxane/water (v/v=1:1), 67.3 g (2.0eq) Boc anhy-dride and 25.3 g sodium dicarbonate(2.0eq) were added in sequence; and an oil bath was employed for solubilizing allthe substrates. The solution was stirred at r.t for 20 hours. After the completion of the reaction, the dioxane was removedunder vacuum, and large number of viscous precipitate was obtained. The precipitate was diluted with 500 mL water, and stirred for another 30 minutes to fully dissolution. The pH of the solution was adjusted to 2 ∼ 3 by 2 N HCl aqueoussolution in ice bath, and the mixture became muddy, and was stilled standing for 30 minutes. The solution was extractedwith AcOEt for 5 times, and the organic phase was combined, dried with MgSO4 overnight. After being filtered, the AcOEtwas removed under vacuum, and 48.6 g yellow oily target compound was obtained with yield of 86percent.