Methanol → methyl (3R)-3-aminobutanoate acetate

Participants

Reaction Steps

Under a nitrogen atmosphere, a mixture of [RuCl2(p-cymene)]2 (0.527 g, 0.861 mmol), (R)-DM-SEGPHOS (1.276 g, 1.77 mmol), and ammonium acetate (0.664 g, 8.61 mmol) was stirred in 1,4-dioxane (10 mL) at 120° C. for 5 hours and then cooled to room temperature. The resultant mixture was added to a mixture of methyl acetoacetate (100.00 g, 861 mmol), ammonium acetate (66.38 g, 861 mmol) and methanol (500 mL) in a 1 L stainless steel autoclave. The reaction mixture was stirred under a hydrogen pressure of 3 MPa at 85° C. for 8 hours. After completion of the reaction, the solvent was removed by evaporation to give methyl (3R)-3-aminobutanoate acetate as a crude material (161.20 g). The crude product was treated with 7N ammonia/methanol and analyzed by GLC using a capillary column TC-5HT, indicating that the yield of methyl 3-aminobutanoate was 87.2%, that of the by-produced methyl 3-hydroxybutanoate was 0.3%, that of the by-produced methyl 3-aminocrotonate was 0.4% and that of the by-produced methyl 3-(2-methoxycarbonyl-1-methyl-1-ethylamino)-2-butenoate was 6.6%. The enantiomeric excess of methyl(3R)-3-aminobutanoate in the crude product was determined to be 94.4% ee by HPLC analysis using a CHIRALCEL OD-H column after conversion into methyl (3R)-3-(4-nitrobenzoylamino)butanoate.

Provenance & Evidence