Synthesis
Step 1: Synthesis of 3-(tert-butoxycarbonyl(methyl)amino)propionic acid
1. a mineral oil suspension of 60% NaH (0.528 g, 13.21 mmol) was washed with hexane (2 x 10 mL) to remove the mineral oil.
2. The washed NaH was suspended in anhydrous THF (6 mL) and the mixture was cooled to 0°C.
3. A solution of Boc-β-alanine (1 g, 5.29 mmol) in anhydrous THF (6 mL) was slowly added with stirring.
4. After 5 min, anhydrous THF (6 mL) solution of iodomethane (0.823 mL, 13.21 mmol) was added dropwise.
5. The reaction mixture was stirred overnight at 0 °C to room temperature.
6. Upon completion of the reaction, the reaction was quenched with ice-cold deionized water (50 mL) and the mixture was washed with ether (25 mL).
7. Separate the aqueous layer and acidify to pH < 2 with concentrated aqueous hydrochloric acid (3 mL).
8. Extract the acidified aqueous layer with ethyl acetate (3 x 20 mL).
9. Combine the organic phases, dry with anhydrous sodium sulfate and concentrate under reduced pressure to afford the target product N-Boc-3-(methylamino)propionic acid (1.095 g, quantitative yield) as a yellow oil.
References
[1] Patent: US2014/66426, 2014, A1. Location in patent: Paragraph 0779
[2] Patent: WO2014/32801, 2014, A1. Location in patent: Page/Page column 157
[3] Journal of Medicinal Chemistry, 1994, vol. 37, # 11, p. 1562 - 1568
[4] Patent: US5428021, 1995, A
