methyl (2S)-2-amino-2-cyclohexylacetate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of N-benzyl-2-(R,S)-(4-cyano-benzyl)-malonamic acid (10 g, 32.4 mmol), (S)-amino-cyclohexyl-acetic acid methyl ester (5.94 g, 34.7 mmol), diisopropylethyl-amine (6.45 ml, 37.9 mmol), 3-hydroxy-3H-benzo[d][1,2,3]triazin-4-one (1.32 g, 8.1 mmol), and dimethylformamide (100 ml) was cooled to 10° C. A solution of dicyclohexyl-carbodiimide (7.83 g, 37.9 mmol) in toluene (10 ml) was added dropwise and the reaction mixture stand over night. The precipitated urea was sucked off, the filtrate was evaporated in vacuo, solved in ethyl acetate, washed with saturated sodium hydrogen carbonate-solution and brine, dried, and evaporated in vacuo. Crystallization from n-heptane/isopropanol gave 9.91 g (66%) of the desired product. mp.: 170-174° C., MS m/z: 462 (M+H)+. the reaction mixture stand over night the filtrate was evaporated in vacuo washed with saturated sodium hydrogen carbonate-solution and brine dried evaporated in vacuo Crystallization from n-heptane/isopropanol

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 3-(4-cyano-phenyl)-2-(R,S)-cyclohexyl-propionic acid (8.8 g, 34.2 mmol, prepared as described in example 1d), (S)-amino-cyclohexyl-acetic acid methyl ester (6.27 g, 36.6 mmol), diisopropylethylamine (6.8 ml, 40.0 mmol), 3-hydroxy-3H-benzo[d][1,2,3]triazin-4-one (1.40 g, 8.6 mmol), and dimethylformamide (200 ml) was cooled to 10° C. A solution of dicyclohexyl-carbodiimide (8.26 g, 40.0 mmol) in toluene (8 ml) was added dropwise over a period of 3 hours and the reaction mixture was stirred for 36 hours. The precipitated urea was sucked off and the filtrate was evaporated in vacuo. Crystallization from n-heptane/isopropanol gave 10.68 g of the desired product, which contained 1,3-dicyclohexyl-urea. The crude material was used without further purification. MS m/z: 411 (M+H)+. the filtrate was evaporated in vacuo Crystallization from n-heptane/isopropanol