Uses
It is a reagent of choice for assignment of absolute configuration of chiral primary amines by 1H NMR, giving better results than Mosher's acid ((R)-(+)-?-Methoxy-?-(trifluoromethyl)-phenyl-acetic acid. αR)-α-[[(1,1-Dimethylethoxy)carbonyl]amino]-benzeneacetic Acid is D-(+)-2-Phenylglycine with Boc protecting group. (αR)-α-[[(1,1-Dimethylethoxy)carbonyl]amino]-benzeneacetic Acid is used as part of a catalyst combination to catalyze regioselective [4 + 2] cycloadditions of β-substituted cyclic enones and polyconjugated malononitriles. It can also be used to catalyze stereoselective preparation of polyfunctional nitrocyclohexene carboxaldehydes.
Synthesis
(1) A mixture of (R)-2-amino-2-phenylacetic acid (200 g, 1.32 mol) and potassium carbonate (218 g, 1.58 mol) was dissolved in a solvent mixture of water (2.0 L) and methanol (0.5 L), and cooled to a temperature of less than 10°C. Di-tert-butyl dicarbonate (288 g, 1.32 mol) was added dropwise, and the reaction was stirred at room temperature after the addition. After the addition, the reaction was stirred at room temperature overnight. After completion of the reaction, the pH of the reaction solution was adjusted to 4-5 with 1 N hydrochloric acid, followed by extraction with ethyl acetate (1.0 L × 3). The organic phases were combined, washed with saturated saline (1.0 L × 1), dried over anhydrous sodium sulfate and concentrated under reduced pressure to give a white solid product (315 g) in 95% yield.
References
[1] Journal of Medicinal Chemistry, 2013, vol. 56, # 20, p. 8049 - 8065
[2] Journal of Medicinal Chemistry, 1991, vol. 34, # 3, p. 968 - 978
[3] Tetrahedron Letters, 1995, vol. 36, # 29, p. 5227 - 5230
[4] Patent: CN104592163, 2016, B. Location in patent: Paragraph 0041; 0042
[5] Patent: CN106748892, 2017, A. Location in patent: Paragraph 0051; 0053; 0054; 0055
