General procedure for the synthesis of (2S,4S)-BOC-4-phenoxypyrrolidine-2-carboxylic acid from methyl (2S,4S)-1-BOC-4-phenoxypyrrolidine-2-carboxylate:
Step 2: Synthesis of (2S,4S)-1-tert-butoxycarbonyl-4-phenoxy-2-pyrrolidine carboxylic acid
Methyl (2S,4S)-1-tert-butoxycarbonyl-4-phenoxy-2-pyrrolidinylcarboxylate (4.31 g, 16.5 mmol) was dissolved in THF (132 ml), followed by addition of 0.25N NaOH solution (132 ml, 33.0 mmol). The reaction mixture was stirred at room temperature overnight. After completion of the reaction, the reaction mixture was concentrated under reduced pressure and the residue obtained was acidified with 1N HCl and subsequently extracted with chloroform. The organic phase was washed with saturated brine and dried over anhydrous sodium sulfate. After removing the solvent by distillation under reduced pressure, the crude product obtained was recrystallized with hexane-chloroform mixed solvent to give (2S,4S)-BOC-4-phenoxypyrrolidine-2-carboxylic acid (2.96 g, 58% yield) as a final white crystalline powder.
1H-NMR (DMSO-d6) δ: 1.36 (s, 9H), 2.16 (d, J = 13.2 Hz, 1H), 2.56 (m, 1H), 3.46 (m, 1H), 3.71 (dt, J = 12.0, 5.4 Hz, 1H), 4.26 (dt, J = 9.5, 7.1 Hz, 1H), 4.99 (m, 1H). 6.85 (m, 2H), 6.94 (t, J = 7.3 Hz, 1H), 7.28 (t, J = 7.3 Hz, 2H).
