(αR)-α-[(Methoxycarbonyl)amino]benzeneacetic acid

To a solution of D-phenylglycine (10.0 g, 66.1 mmol) and NaOH (21.2 g, 265 mmol) in water (60 niL) at 0To a 0°C solution of D-phenylglycine (10.0 g, 66.1 mmol) and NaOH (21.2 g, 265 rnmol) in water (60 mL) was added methyl chloroformate (10.2 mL, 133 mmol) dropwise over 20 minutes. The resulting reaction was allowed to stir at 0°C for 1 hour and then acidified with concentrated hydrochloric acid (25 mL, 300 mmol). The acidic solution was extracted with EtOAc (3 x 100 mL) 3/4nd the combined organic extracts were dried over MgS0To a solution of D-phenylglycine (10.0 g, 66.1 mmol) and NaOH (21.2 g, 265 mmol) in water (60 mL) at 0 °C was added methyl chloroformate (10.2 mL, 133 mmol) dropwise over 20 minutes. The resulting mixture was allowed to stir at 0 °C for 1 hour, then was acidified using concentrated hydrochloric acid (25 mL, 300 mmol). The acidic solution was extracted with EtOAc (3 x 100 mL) and the combined organics were dried over MgS0To a solution of D-phenylglycine (10.0 g, 66.1 mmol) and NaOH (21.2 g, 265 mmol) in water (60 mL) at 0 °C was added methyl chloroformate (10.2 mL, 133 mmol) dropwise over 20 minutes. The resulting mixture was allowed to stir at 0 °C for 1 hour, then was acidified using concentrated hydrochloric acid (25 mL, 300 mmol). The acidic solution was extracted with EtOAc (3 x 100 mL) and the combined organics were dried over MgS0To a solution of D-phenylglycine (10.0 g, 66.1 mmol) and NaOH (21.2 g, 265 mmol) in water (60 mL) at 0 °C was added methyl chloroformate (10.2 mL, 133 mmol) dropwise over 20 minutes. The resulting reaction was allowed to stir at 0 °C for 1 hour, then was acidified using concentrated hydrochloric acid (25 mL, 300 mmol). The acidic solution was extracted with EtOAc (3 x 100 mL) and the combined organics were dried over MgS0EXAMPLE 2Preparation of Intermediate Compound Int-2a To a solution of D-phenylglycine (10.0 g, 66.1 mmol) and NaOH (21.2 g, 265 mmol) in water (60 mL) at 0 °C was added methyl chloroformate (10.2 mL, 133 mmol) dropwise over 20 minutes. The resulting mixture was allowed to stir at 0 °C for 1 hour, then was acidified using concentrated hydrochloric acid (25 mL, 300 mmol). The acidic solution was extracted with EtOAc (3 x 100 mL) and the combined organics were dried over MgS0EXAMPLE 2Preparation of Intermediate Compound Int-2a To a solution of D-phenylglycine (10.0 g, 66.1 mmol) and NaOH (21.2 g, 265 mmol) in water (60 mL) at 0 °C was added methyl chloroformate (10.2 mL, 133 mmol) dropwise over 20 minutes. The resulting mixture was allowed to stir at 0 °C for 1 hour, then was acidified using concentrated hydrochloric acid (25 mL, 300 mmol). The acidic solution was extracted with EtOAc (3 x 100 mL) and the combined organics were dried over MgS0D-(-)-α-Phenylglycine (0.165 mmol) was dissolvedin tetrahydrofuran (500 mL), followed by the addition of NaHCO3 (0.496 mmol) in water (500 mL), and then theaddition of methylchloroformate (0.182 mmol) at room temperature. The reaction mixture was stirred at room temperatureovernight. The mixture was acidified to pH = 3 with HCl (1N) and the volatile was concentrated in vacuo. The aqueouslayer was extracted with ethyl acetate and the organic layer was dried over MgSO4, filtered, and concentrated in vacuoto give compound 31 as a pale yellow solid in 80percent yield. MS (ESI, EI+) m/z = 209 (MH+).5.1.1.1 General procedure: NaSodium carbonate (0.55 g, 5.2 mmol) Was added to D-phenylglycine (1.500 g, 10.0 mmol) Of sodium hydroxide aqueous solution (10 mL of 1 M / H 2 O, 10 mmol) The reaction mixture was cooled in an ice-water bath. Methylene chloroformate (0.85 mL, 11.0 mmol) was added in small portions, The ice bath was removed and the reaction mixture was stirred at room temperature for 3.25 hours. The reaction mixture was washed with ether (3 X 18 mL) and the water layer was cooled in an ice bath and then acidified to pH 1-2 by addition of con.HCl and extracted with dichloromethane (3 X 18 mL) . The organic layer was dried over anhydrous magnesium sulfate, filtered, concentrated in vacuo and the resulting oil residue was treated with diethyl ether / hexane (5/4, 10 mL) to give a precipitate. The resulting precipitate was filtered, washed with diethyl ether / hexane (1/3) and then dried under vacuum to obtain the target compound (R) -2- (methoxycarbonylamino) -2- phenylacetic acid (1.4 g, 67percent yield) as a white solid.Example 6 (R)-2-(methoxycarbonylamino)-2-phenylacetic acidTFA (16 mL) was added dropwise to a cooled (ice/water) CH2Cl2 (160 mL) solution of the above product over7 minutes, and the cooling bath was removed and the reaction mixture was stirred for 20 hours. Since the deprotectionwas still not complete, an additional TFA (1.0 mL) was added and stirring continued for an additional 2 hours. The volatile component was removed in vacuo, and the resulting oil residue was treated with diethyl ether (15 mL) and hexanes (12mL) to provide a precipitate. The precipitate was filtered and washed with diethyl ether/hexanes (∼1:3 ratio; 30 mL) anddried in vacuo to provide Cap-4 as a fluffy white solid (5.57 g). Optical rotation: -176.9° [c=3.7 mg/mL in H2O; λ=589nm]. 1H NMR (DMSO-d6, δ=2.5 ppm, 400 MHz): δ 12.84 (br s, 1H), 7.96 (d, J=8.3, 1H), 7.41-7.29 (m, 5H), 5.14 (d, J=8.3, 1H), 3.55 (s, 3H). LC (Cond. I): RT=1.01 min; >95 percent homogeneity index; LC/MS: Anal. Calcd. for [M+H]+C10H12NO4210.08; found 210.17; HRMS: Anal. Calcd. for [M+H]+C10H12NO4 210.0766; found 210.0756.