2-AMINO-2-(4-METHYLPHENYL)ACETIC ACID

The crude step-a product (17 g) was dissolved 6N HCI (136 ml_) and refluxed for 20 h. HCI was removed under reduced pressure. The residue was diluted with EtOH (2 x 200 ml_) and concentrated under reduced pressure. Finally ethyl acetate (250 ml.) was added and stirred at 7O0C for 1 hour. A solid came out upon cooling and it was filtered through glass-sintered funnel to afford yellow crystalline solid compound (15 g, crude). Step c: Step-b product (15 g, 74.4 mmol) was dissolved in HCI (300 mL) and it was cooled to -50C. Sodium nitrite solution (9.75 g, 141.3 mmol) in water (45 mL) was added dropwise over the period of 30 minutes. After complete addition, reaction mixture was stirred at ambient temperature for 3 h. TLC (in ethyl acetate Rf = 0.3) showed complete consumption of starting material. The aqueous part was extracted in ethyl acetate (3 x 250 mL). The organic layer was washed with water (2 x 200 mL) and finally with brine (200 mL). The washed organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to afford a yellow solid (12.5 g, crude).Substitution in the procedure of Example 3 for the N-tert.-butoxycarbonyl derivative of D-alpha-aminophenylacetic acid (also called D-alpha-tert.-butoxycarboxamidophenylacetic acid) of an equimolar weight of the N-tert.-butoxycarbonyl derivative of D-alpha-amino-2-thienylacetic acid, D-alpha-amino-3-thienylacetic acid, d-alpha-amino-m-nitrophenylacetic acid, D-alpha-amino-p-methylphenylacetic acid, D-alpha-amino-m-methylphenylacetic acid, D-alpha-amino-p-chlorophenylacetic acid, D-alpha-amino-m-chlorophenylacetic acid, D-alpha-amino-p-fluorophenylacetic acid, D-alpha-amino-m-fluorophenylacetic acid, ...