N-tert-Butoxycarbonyl-DL-tryptophan

Synthesis

Step 3. General procedure for the preparation of BOC-D-tryptophan. To a solution of water (54 mL) containing NaOH (2.2 g, 55.0 mmol) was added DL-tryptophan (10.0 g, 49.0 mmol) and 1,4-dioxane (36 mL). Subsequently, di-tert-butyl dicarbonate (Boc2O, 10.7 g, 49.1 mmol) was added slowly and dropwise to the above mixture. The reaction mixture was stirred at room temperature for 24 hours. The progress of the reaction was monitored by thin layer chromatography (TLC) and the completion of the reaction was indicated by the unfolding of dichloromethane: methanol = 10:1 and an Rf value of 0.5. The reaction mixture was adjusted to pH 6.0 with solid citric acid and subsequently extracted with ethyl acetate (EtOAc, 30 mL x 3). The organic layers were combined, dried and concentrated to give a colorless oil. The residue was washed with petroleum ether (100 mL) and filtered, and the filter cake was further washed with petroleum ether and dried to give BOC-D-tryptophan (14.8 g, 99.0% yield) as a final white solid.

References

[1] Patent: WO2014/14937, 2014, A1. Location in patent: Paragraph 0125; 0128
[2] Patent: CN104876930, 2017, B. Location in patent: Paragraph 0054-0056
[3] Patent: US2010/297756, 2010, A1
[4] Chemistry - A European Journal, 2015, vol. 21, # 51, p. 18589 - 18593
[5] European Journal of Medicinal Chemistry, 2018, vol. 145, p. 140 - 153