(+/-)-BOC-ALPHA-PHOSPHONOGLYCINE TRIMETHYL ESTER

Step 1: In a round-bottomed flask equipped with a reflux condenser, a suspension of Cbz methoxyglycine methyl ester 35 (5.98 g, 23.6 mmol) in toluene (25 mL) was heated to 70C under nitrogen with stirring to dissolve the solids. Phosphorus trichloride (freshly distilled) was added (1.96) mL, 23.6 mmol) and the reaction was stirred at 70C for 24 hours. Add trimethyl phosphite (2.08 ) mL, 23.6 mmol) and the reaction was stirred at 70C for 3 hours. The solvent was evaporated and the residue was dissolved in EtOAc (50 mL). The residue was diluted with ice-cold saturated NaHCO3 (3 x 10) mL), water (10 mL), and brine (25 mL) to wash the organic solution and then dried with anhydrous MgSO4. The solvent was removed and the residue was recrystallized from EtOAc/hexane to give 7.03 g (90%) white powder ()-BOC-A-phosphorylglycine trimethyl ester. mp 78 degrees Celsius.

Step 2: Phosphoglycerol ester 36 (2.00 g, 6.04 mmol) and di-tert-butyl dicarbonate were dissolved in methanol (15 mL) in a Parr shaker hydrogenation flask and degassed with N2 for 15 min. Carbon-loaded palladium (10%, 100 ) was added. mg) and the solution was shaken for 3 h at room temperature under 40 psi H2. The solvent was concentrated and the residue dissolved in EtOAc (30 mL). The solution was diluted with saturated NaCO3 (3 x 10 ) mL), water (10 mL) and brine (20 mL) to wash the organic solution and then dried over MgSO4. The solvent was concentrated and the product precipitated by the addition of hexane to give 1.55 g (86%) white solid ()-BOC-A-phosphorylglycine trimethyl ester.