4-tert-Butoxycarbonylamino-1-methyl-1H-pyrrole-2-carboxylic acid

Chemical Properties

White crystalline powder

Uses

4-(Boc-amino)-1-methylpyrrole-2-carboxylic Acid is an unnatural amino acid for preparing heteroaromatic oligoamides for regulating gen expression in biotechnology.

Synthesis

To methyl 4-((tert-butoxycarbonyl)amino)-1-methyl-1H-pyrrole-2-carboxylate (5.0 g, 19.67 mmol) was added 30 mL of an aqueous solution containing 8 g of sodium hydroxide in 120 mL of a 1:1 solvent mixture of tetrahydrofuran (THF) and water. The reaction mixture was stirred at room temperature overnight. Upon completion of the reaction, the mixture was concentrated to remove THF, diluted with water, and then extracted with a solvent mixture of ethyl acetate/hexane (1:1). The aqueous phase was adjusted to pH 4.0 with 20% phosphoric acid and subsequently extracted with ethyl acetate (4 x 60 mL). The organic phases were combined, dried with anhydrous magnesium sulfate, filtered and the solvent evaporated to give the crude product. The crude product was crystallized by ethanol/ethyl acetate/hexane mixed solvent to give 3.81 g (81% yield) of 4-[(tert-butoxycarbonyl)amino]-1-methyl-1H-pyrrole-2-carboxylic acid. The product was characterized by 1H NMR (CD3OD) δ 12.79 (s, 1H), 10.48 (br, 1H), 7.51 (s, 1H), 6.99 (s, 1H), 3.78 (s, 3H), 1.49 (s, 9H); 13C NMR δ 158.47, 153.82, 123.64, 121.56, 109.58, 79.52, 37.06, 28.42; MS m/z 239.2 (M-H) confirmed.

References

[1] Journal of Organic Chemistry, 2004, vol. 69, # 23, p. 8151 - 8153
[2] Journal of Pharmaceutical Sciences, 1989, vol. 78, # 11, p. 910 - 917
[3] Patent: WO2010/91150, 2010, A1. Location in patent: Page/Page column 141
[4] Journal of the American Chemical Society, 1996, vol. 118, # 26, p. 6141 - 6146
[5] Chemistry - A European Journal, 2007, vol. 13, # 11, p. 3177 - 3186