Synthesis
The general procedure for the synthesis of 2-((tert-butoxycarbonyl)amino)-2-methylpropionic acid from di-tert-butyl dicarbonate and 2-aminoisobutyric acid is as follows:
Preparation of Example 26: 2-(tert-butoxycarbonylamino)-2-methylpropionic acid
200 mg (1.94 mmol) of 2-amino-2-methylpropionic acid was dissolved in a solvent mixture of 8.0 mL of 1.0 N NaOH solution and 8.0 mL of 1,4-dioxane, followed by the addition of 846 mg (3.88 mmol) of di-tert-butyl dicarbonate (Boc2O). The reaction mixture was stirred at room temperature for 16 hours. Upon completion of the reaction, 1,4-dioxane was removed by distillation under reduced pressure. The residue was adjusted to pH 3 with 1N HCl solution and then extracted with 320 mL of ethyl acetate. The organic phase was dried with anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to give 315 mg of the white solid product 2-(tert-butoxycarbonylamino)-2-methylpropanoic acid in 80% yield.
The product was characterized by 1H NMR (400 MHz, CDCl3): δ 5.07 (brs, 1H), 1.54 (s, 6H), 1.45 (s, 9H).
References
[1] Bulletin of the Chemical Society of Japan, 1987, vol. 60, # 4, p. 1391 - 1397
[2] Angewandte Chemie - International Edition, 2018, vol. 57, # 20, p. 5679 - 5683
[3] Angew. Chem., 2018, vol. 130, p. 5781 - 5785,5
[4] Patent: US2015/210635, 2015, A1. Location in patent: Paragraph 0502-0504
[5] Patent: EP2865664, 2015, A1. Location in patent: Paragraph 0118; 0119
