Synthesis
The general procedure for the synthesis of (2S,5S)-N-Boc-5-methylpyrrolidine-2-carboxylic acid from the compound (CAS: 676560-83-1) is as follows:
1. ethyl (2S,5S)-1-(tert-butoxycarbonyl)-5-methylpyrrolidine-2-carboxylate (6.46 g, 25.1 mmol) was dissolved in ethanol (20 mL).
2. Lithium hydroxide monohydrate (2.11 g, 50.2 mmol) and deionized water (12 mL) were added to the above solution.
3. The reaction mixture was stirred at room temperature for 16 hours. 4.
4. Upon completion of the reaction, the mixture was partitioned between ethyl acetate and a 1:1 mixture of saturated aqueous sodium chloride solution and 1N hydrochloric acid.
5. The aqueous layer was separated and extracted again with ethyl acetate.
6. Combine all organic layers and dry with anhydrous sodium sulfate.
7. Vacuum removal of the solvent afforded (2S,5S)-1-(tert-butoxycarbonyl)-5-methylpyrrolidine-2-carboxylic acid as a white solid (quantitative yield), which was used directly in the next reaction without further purification.
References
[1] Patent: US2014/178336, 2014, A1. Location in patent: Paragraph 0252
[2] Patent: US2015/361087, 2015, A1. Location in patent: Paragraph 0311; 0316
[3] Patent: WO2015/110048, 2015, A1. Location in patent: Paragraph 00165
[4] Patent: US2017/44140, 2017, A1. Location in patent: Paragraph 0218; 0231; 0232; 0233
[5] Journal of Medicinal Chemistry, 2006, vol. 49, # 12, p. 3520 - 3535
