L-Cyclohexylalanine

white to light yellow crystal powder

Production of L-cyclohexylalanine 20 g (121 mmol) L-phenylalanine are dissolved or suspended in 200 ml deionised water, 200 ml isopropanol and 12.2 ml (146 mmol) 37 percent hydrochloric acid. After addition of 2 g of the Pt/Rh catalyst, 4 percent Pt + 1 percent Rh on activated carbon (water content approx. 50 percent, corresponding to approx. 5 wt. percent catalyst relative to L-phenylalanine used), the reaction mixture is introduced into a 1 1 hydrogenation autoclave. After being rendered inert with nitrogen three times, it is rinsed with hydrogen twice, then a hydrogen overpressure of 8-10 bar is established and the reaction solution heated to 50-60°C. After approximately 6 to 8 hours, hydrogen uptake is completed (theoretical amount of H2 8.1 1). The hydrogenator is depressurised and once again rendered inert with nitrogen three times. The still hot reaction solution is extracted with a nutsch filter and the catalyst is washed with 50 ml deionised water. The filtrate is first concentrated to low volume in vacuo (the isopropanol largely removed), the residue then adjusted to a pH of 5-6 with 50percent sodium hydroxide solution. It is cooled to a temperature of 0-10°C, the product is extracted with a nutsch filter, rinsed with 50 ml deionised water and dried in a drying oven in vacuo at 50- 70°C. Yield: 19.5 g (94.2 percent) H-NMR (500 MHz, D20/NAOD) : 8 (PPM) = 0. 85-1. 0 AND 1.1-1. 52 and 1.63-1. 75 (each m, together 13H, cyclohexyl-H and CYCLOHEXYL-CH2), 3.3 (t, 1 H, A-H)The selective hydrogenation of the optically active phenyl amino acid was carried out in a magnetically stirred stainless-steel autoclave (100 ml). Prior to the loading of the catalyst, the autoclavewas purged three times with hydrogen to expel the air. Typically, a freshly prepared suspension of nanoRu(at)hectorite (0.01592 mmol Ru, 10 ml H2O) and the appropriate amount of the substrate were carefully transferred into the autoclave under inert atmosphere, and then the autoclave was charged with H2 to the desired pressure. The autoclave was placed into the pre-heated heating mantle and the magnetic stirring was started for the indicated reaction time. After the reaction, the autoclave was cooled down and the pressure was released. The reactor was thoroughly rinsed with 2 N NaOH solution to wash out the entire product (in the case of acidic system, 2 N HCl was used). All the collected solutions were filtered (0.22 mm, PTFE) to remove the catalyst and then treated with diluted HCl (or NaOH) solution to adjust the pH to 5.5, which caused the partial precipitation of the product. The suspensionwas then reduced in vacuo to 10 ml in order to complete the precipitation. The precipitate was filtered off, washed with distilled water and dried in vacuo for 24 h.L-phenylalanine was added to 200 mL of water, 200 mL of isopropanol, 12.2 mL of hydrochloric acid having a concentration of 37percent and 2 g of Pt/Rh(4:1) carbon having a concentration of 50percent were added, hydrogen was introduced to the system, the pressure of the system was maintained at 8 to 10 bar, reaction was performed at 50° C. to 60° C. for 6 to 8 h. Then the system was filterred and washed with 50 mL of water, a filtrate was concentrated and then the pH value of the filtrate was regulated to 5 to 6 with sodium hydroxide having a concentration of 50percent. Then the temperature was cooled to 0 to 10° C., suction filtration was performed to obtain a solid and wash the solid with 20 mL of water, then vacuum drying was performed at 50 to 70° C., General procedure: A mixture of pyridoxamine 4a (2.1 mg, 0.0050 mmol), 4-(naphthalen-1-yl)-2-oxobutanoic acid (1a) (22.8 mg, 0.10 mmol), 2, 2-diphenylglycine 11 (22.7 mg, 0.10 mmol), CH3COOH (48.0 mg, 0.80 mmol), EtOH (0.40 mL), and H2O (0.10 mL) was stirred at 25 °C for 24 h. The reaction mixture was transferred to a 25-mL eggplant-shaped flask. Methanol (10 mL) was added to dissolve the solid completely and silica gel (0.50 g) was added. The solvent was removed under reduced pressure at 25 oC. The residue was submitted to flash column chromatography (silica gel, EtOH / ethyl acetate / 25-28percent ammonia solution = 100:58:16) to give amino acid 2a (22.0 mg, 96percent yield, 83percent ee) as a white solid. The enantiomeric excess (ee) of 2a was determined by HPLC analysis after the amino acid was converted to the corresponding methyl ester by treatment with diazomethane in methanol at room temperature (Chiralcel OD-H, Hex:i-PrOH = 85:15, 1.0 mL/min). The enantiomeric excesses (ee’s) of products 2b-l and 2o and the dr values of products 2m-n were determined by HPLC analysis after the amino acids were converted to the corresponding N-benzoyl methyl esters by treatment with thionyl chloride in methanol and subsequent reaction with benzoic anhydride.To a 5 mL vial equipped with a magnetic stirrer bar were added 3-cyclohexyl-2-oxopropanoic acid (1j) (0.0510 g, 0.30 mmol), 2, 2-diphenylglycine (2) (0.0681 g, 0.30 mmol), chiral pyridoxamine 6g (0.0195 g, 0.030 mmol), and MeOH-H2O (8:2) (3.0 mL). The mixture was stirred at 20 °C for 3 days. The reaction mixture was transferred to a 25 mL round-bottom flask and MeOH was added until all the solid was dissolved. Then silica gel (0.50 g) was added. After removal of the solvent in vacuo at 20 °C, the resulting residue was submitted to column chromatography on silica gel (EtOH/ethyl acetate/25-28percent ammonia solution =100:58:16) to give compound 3j (0.0401 g, 78percent yield, 52percent ee) as a white solid. The enantiomeric excesses of 3b-k were deteremined by HPLC analysis after being converted to N-benzoyl methyl esters by treatment with thionyl chloride in methanol and subsequent reaction benzoyl chloride.7 The enantiomeric excess of 3a was deteremined by HPLC analysis after being converted to its methyl ester by treatment with CH2N2 in methanol.

Molecular Weight:171.24
XLogP3:-0.3
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:3
Exact Mass:171.125928785
Monoisotopic Mass:171.125928785
Topological Polar Surface Area:63.3
Heavy Atom Count:12
Complexity:153
Defined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes