Synthesis
Step 1: Synthesis of methyl (R)-2-(isopropylamino)butyrate; Methyl (R)-2-aminobutyrate (28.78 g, 0.19 mol) was dissolved in 200 mL of dichloromethane, followed by the addition of acetone (11.96 g, 0.21 mol) and sodium acetate (30.76 g, 0.38 mol), and stirred for 3 hours at room temperature. Sodium triacetoxyborohydride (59.61 g, 0.28 mol) was added to the reaction mixture and stirring was continued for 12 hours. Upon completion of the reaction, 100 mL of 1 M hydrochloric acid was added and the pH was adjusted slowly and dropwise to 8-9 by adding saturated sodium carbonate solution. the reaction mixture was extracted with dichloromethane (100 mL x 3) and the organic phases were combined. The organic phase was washed with saturated sodium chloride solution (50mL×3), dried with anhydrous magnesium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography to afford methyl (R)-2-(isopropylamino)butyrate (16.40 g, yield 55.0%) as a light yellow oily liquid.
References
[1] Patent: EP2481739, 2012, A1. Location in patent: Page/Page column 57
[2] Patent: US2012/184543, 2012, A1. Location in patent: Page/Page column 58-59
[3] Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 9, p. 2743 - 2749
[4] Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 5, p. 1311 - 1315
[5] Journal of Medicinal Chemistry, 2018, vol. 61, # 17, p. 7785 - 7795
