L-CYCLOPROPYLALANINE

3a (S)-beta-Cyclopropylalanine Tert-Butyl Ester 3.5 g (27.1 mmol) of (S)-beta-cyclopropylalanine were added to a mixture of 50 mL of dioxane and 5 ml of concentrated sulfuric acid (prepared by cautious addition of the acid dropwise to dioxane at 5° C.) at room temperature. The solution was transferred into a sealing tube into which 40 ml of isobutylene were condensed at -78° C. The sealed tube was then shaken at room temperature on a shaker for 24 hours. After the sealed tube had been opened (while cooling), the reaction mixture was cautiously introduced into a stirred mixture of 30 mL of triethylamine and 50 mL of water cooled to 0° C. After removal of excess isobutylene, the product was extracted with ether (2*50 mL). Drying of the ether phases over magnesium sulfate, filtration and removal of the solvent in vacuo resulted in the crude product (pale yellow oil), which was employed without further purification in the subsequent reaction. Yield 4.2 g (84percent). 1H NMR (CDCl3): delta 0.10 (m, 2H, CH2), delta 0.49 (m, 2H, CH2), delta 0.81 (m, 1H, CH), delta 1.25 (br. m, 2H, NH2), delta 1.50 (s, 9H, (CH3)3), delta 1.61 (m, 2H, CH2), delta 3.41 ppm (dd, 1H, N-CH)Step A 2-(S)-Hydroxy-3-(cyclopropyl)propanoic acid A 1 L, 3-neck flask was equipped with two dropping funnels, one containing 21.3 mL of 2.0 N H2SO4 and the other containing 21.3 mL of 2.0 N NaNO2. A mixture of 5.00 g (38.7 mmol) of 2-(S)amino-3-(cyclopropyl)propanoic acid in 28 mL of H2O at 0° C. was treated with a sufficient amount of the acid solution to dissolve the solid. The remaining H2SO4 solution and the NaNO2 solution were added, maintaining the internal temperature at less than 5° C. The resulting mixture was stirred cold for 3 h, then warned to rt and stirred for 20 h. The reaction mixture was saturated with NaCl and extracted with 4*100 mL of EtOAc. The extracts were dried over MgSO4 and concentrated to afford 4.30 g (85percent) of the title compound: 1H NMR (300 MHz) delta 0.13-0.18 (m, 2H), 0.48-0.54 (m, 2H), 0.89 (m, 1H), 1.67-1.76 (m, 2H), 4.37 (dd, J=6.4, 4.7 Hz, 1H).General procedure: Thestartingamino acid (1.0 eq)was dissolved in MeOH (2-4 mL/1 mmol), and catalytic 98percentsulfuric acid (~0.1 eq) was then added. The mixture was heated to refluxovernight. The reaction solution was cooled to room temperature andconcentrated in vacuo. The resulting crude residue was dissolved in a sat.NaHCO3 (aq) solution, and extracted with EtOAc. The combined organiclayers were washed with sat. NaHCO3 (aq) and brine, dried over MgSO4and concentrated to afford the desired ester. 14-100percent