Uses
Morpholine-3,4-dicarboxylic acid 4-tert-butyl ester is an organic heterocyclic compound that can be used in decarboxylation arylation reactions to prepare other compounds. It is also used as a synthetic intermediate component in the preparation of substances such as thienopyrrole compounds, pyridine derivatives and cyclised acetamide derivatives.
Synthesis
The general procedure for the synthesis of 4-Boc-3-morpholinecarboxylic acid from 3-morpholinecarboxylic acid and di-tert-butyl dicarbonate is as follows: di-tert-butyl dicarbonate (3.33 g, 15.3 mmol) was slowly added to acetone (5 mL) and water (0 mL) containing morpholine-3-carboxylic acid (1.7 g, 10.2 mmol), potassium carbonate (7.04 g, 51 mmol) in a 0°C in a mixed solution. The reaction mixture was stirred at room temperature for 24 hours. After completion of the reaction, the reaction solution was diluted with water (50 mL) and extracted with ether (2 x 50 mL). The aqueous phase was acidified with 2M aqueous hydrochloric acid (100 mL) and then extracted with dichloromethane (2 x 50 mL). The organic phases were combined, washed sequentially with water (50 mL) and brine (50 mL), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give the white solid product 4-Boc-3-morpholinecarboxylic acid (1.98 g, 84% yield). The product was characterized by 1H NMR (CDCl3), δ (ppm): 4.46 (m, 2H), 3.80 (m, 3H), 3.53 (m, 1H), 3.31 (m, 1H), 1.48 (d, 9H).
References
[1] Patent: WO2005/80386, 2005, A1. Location in patent: Page/Page column 40
[2] Angewandte Chemie - International Edition, 2018,
[3] Angew. Chem., 2018, vol. 130, # 44, p. 14768 - 14773,6
[4] Patent: WO2009/67233, 2009, A1. Location in patent: Page/Page column 46-47
