Uses
3-((tert-Butoxycarbonyl)amino)-3-methylbutanoic Acid is an intermediate used in the synthesis of (2E)-5-(tert-Butyloxycarbonylamino)-5-methylhex-2-enoic Acid (B809765), which is used in the preparation of C-terminal sulfonamide analogs of NN703 as growth hormone secretagogues.
Synthesis
Di-tert-butyl 3-amino-3-methylbutyrate (0.59 g, 5.04 mmol) and di-tert-butyl dicarbonate (1.228 mL, 5.29 mmol) were added to a 1 M potassium hydroxide solution (5.04 mL, 5.04 mmol) as a raw material after dissolving in dioxane (10 mL). The reaction mixture was stirred at room temperature for 16 hours. Upon completion of the reaction, the dioxane was removed by distillation under reduced pressure. The residue was diluted with water (20 mL) and the pH was adjusted with lithium hydroxide to 13. Subsequently, the mixture was washed three times with ether. Next, the pH was adjusted to 3 with 2N hydrochloric acid to obtain a turbid solution. The solution was extracted four times with ethyl acetate and the combined organic phases were washed with a small amount of brine and dried with anhydrous sodium sulfate. Finally, N-Boc-3-amino-3-methylbutyric acid (860 mg, 3.96 mmol, 79% yield) was obtained as a crystalline solid by vacuum concentration.
References
[1] Patent: US2010/204274, 2010, A1. Location in patent: Page/Page column 30
[2] Patent: US2012/316147, 2012, A1. Location in patent: Page/Page column 43
[3] Patent: WO2012/168350, 2012, A1. Location in patent: Page/Page column 98; 99
[4] Patent: WO2017/68089, 2017, A2. Location in patent: Page/Page column 321
[5] Patent: WO2017/216726, 2017, A1. Location in patent: Page/Page column 650
