Example 7: Synthesis of tert-butyl (1R,2S)-2-((S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidine-1-carbonyl)cyclopentylcarbamate
Step 1: Preparation of (1S,2R)-2-(tert-butoxycarbonylamino)cyclopentanecarboxylic acid
At 25 °C, (1S,2R)-2-aminocyclopentanecarboxylic acid hydrochloride (515 mg, 3.11 mmol) was dissolved in water (5.00 mL) and stirred until completely dissolved. Subsequently, potassium hydroxide (349 mg, 6.22 mmol) was added. Then, a solution of di-tert-butyl dicarbonate (0.722 mL, 3.11 mmol) in dioxane (5 mL) was added dropwise to the reaction system. The reaction mixture was stirred continuously for 20 hours at room temperature. Upon completion of the reaction, the mixture was concentrated to remove the organic solvent. The remaining aqueous phase was extracted with chloroform three times (same amount each time). The chloroform extracts were combined, dried with anhydrous sodium sulfate, filtered and concentrated to afford (1S,2R)-2-(tert-butoxycarbonylamino)cyclopentanecarboxylic acid (550 mg, 2.399 mmol, 77% yield) as a colorless viscous oil. The mass spectrum (ESI+) showed m/z = 230.30 ([M + H]+).
