Synthesis
The general procedure for the synthesis of (2S,3aS,7aS)-1-(tert-butoxycarbonyl)octahydro-1H-indole-2-carboxylic acid from di-tert-butyl dicarbonate and L-octahydroindole-2-carboxylic acid is as follows: L-octahydroindole-2-carboxylic acid (1.69 g, 10 mmol) was placed in a reaction flask, and 30 mL of tetrahydrofuran (THF) and 30 mL of distilled water was added and stirred until completely dissolved. Subsequently, 7 mL of aqueous sodium hydroxide (0.68 g, 17 mmol) was added dropwise to the reaction mixture while the reaction flask was cooled in an ice bath. After the dropwise addition, the reaction mixture was continued to be stirred for 10 minutes. Then, di-tert-butyl dicarbonate (Boc) 2O (2.84 g, 13 mmol) was added to the reaction system, gradually warmed up to room temperature and the reaction was continuously stirred for 12 hours. The progress of the reaction was monitored by thin layer chromatography (TLC) and after confirming the completion of the reaction, the reaction mixture was diluted with distilled water. Impurities were removed by extraction with methyl tert-butyl ether (MTBE) and the aqueous phase was adjusted to acidity (pH ≈ 3) with citric acid. Next, the aqueous phase was extracted three times with ethyl acetate and the organic phases were combined. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, filtered and concentrated to afford 3.21 g of the target compound (2S,3aS,7aS)-1-(tert-butoxycarbonyl)octahydro-1H-indole-2-carboxylic acid in 100% yield.
References
[1] Patent: CN106083829, 2016, A. Location in patent: Paragraph 0061; 0065; 0067; 0068
[2] Patent: WO2004/92132, 2004, A1. Location in patent: Page 85
[3] European Journal of Organic Chemistry, 2008, # 5, p. 934 - 940
[4] Patent: WO2004/92132, 2004, A1. Location in patent: Page 80-81
[5] Bioorganic and Medicinal Chemistry, 2014, vol. 22, # 23, p. 6684 - 6693
