Bromo-tert-butoxycarbonylamino-acetic acid tert-butyl ester (1.5 g, 4.8 mmol) was dissolved in 40 mL of dichloromethane and then cooled in a dry ice/acetone bath. A solution of methyl trimethylsilyl dimethylketene acetal (1.9 mL, 9.6 mmol) in dichloromethane (5 mL) was added, followed by slow addition of a solution of titanium (IV) chloride (0.57 mL, 5.28 mmol) in dichloromethane (5 mL), and then a solution of triethylamine (0.73 mL, 5.28 mmol) in dichloromethane (10 mL). The reaction mixture was warned to room temperature with stirring over 16 h. An aqueous solution of citric acid (˜11 g/100 mL) was added and the reaction mixture briefly stirred. The layers were separated and the aqueous layer was extracted once more with dichloromethane. The combined dichloromethane layers were washed with sodium bicarbonate solution and dried over sodium sulfate. After evaporation, the residue was purified by silica gel chromatography (ethyl acetate/hexanes) to give 206 mg (13%) of 3-tert-butoxycarbonylamino-2,2-dimethyl-succinic acid 4-tert-butyl ester 1-methyl ester.
