The general procedure for synthesizing D-cyclohexylglycine from levophenylglycine is as follows:
Example 1: Preparation of D-cyclohexylglycine
100 g (661.5 mmol) of D-phenylglycine was dissolved or suspended in a mixture of 890 ml of deionized water, 290 ml of isopropanol and 66.7 ml (802 mmol) of 37% hydrochloric acid. 10 g of Pt/Rh catalyst (4% Pt + 1% Rh loaded on activated carbon with about 50% water, corresponding to about 5 wt% of the amount of D-phenylglycine) was added. The reaction mixture was transferred to a 2 liter hydrogenation autoclave. It was displaced three times with nitrogen and then flushed twice with hydrogen, after which a hydrogen pressure of 8-10 bar was established and the reaction system was heated to 50-60°C. After about 6 to 8 hours of reaction, the hydrogen uptake was complete (theoretical H2 uptake of 44.4 L). The hydrogen was released by depressurization and again replaced three times with nitrogen. The reaction solution was filtered while hot and the catalyst was washed with 200 ml of deionized water. The filtrate was first adjusted to pH 2-2.5 with 50% sodium hydroxide solution at 40-60°C, at which point crystals began to precipitate. The pH was maintained and stirred for 15-30 min, then adjusted to pH 5-6 with 50% sodium hydroxide solution.The reaction mixture was cooled to 0-10 °C in an ice bath, the product was collected by filtration, washed with 300 ml of deionized water and dried in a vacuum oven at 50-70 °C. The catalyst can be reused for several times without any problem. The catalyst can be reused several times without deactivation.
Yield: 100-102 g (95.8-97.7% yield).
1H-NMR (500 MHz, D2O/NaOD): δ (ppm) = 1-1.26 and 1.53-1.75 (both m, combined 11H, cyclohexyl proton), 3.02 (d, 1H, α-proton).
The enantiomeric purity of the resulting D-cyclohexylglycine was consistent with that of the starting material D-phenylglycine by chiral GC analysis.
