N-Piperidinoethanol → (3R,4S)-3-amino-4-(3-boronopropyl)-1-(2-(piperidin-1-yl)ethyl)pyrrolidine-3-carboxylic acid

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A cooled (0° C.) solution of N-(2-hydroxyethyl)piperidine (90.5 mg, 0.70 mmol) and diisopropylethylamine (0.30 mL, 1.7 mmol) in anhydrous acetonitrile (12 mL) under nitrogen was treated with methanesulfonyl chloride (80.2 mg, 0.70 mmol), stirred 2 h, and treated with (3R,4S)-3-acetamido-N-tert-butyl-4-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propyl)pyrrolidine-3-carboxamide (Example 8, step 4) (198 mg, 0.5 mmol) and heated to 60° C. for 15 h. The reaction mixture was concentrated, deprotected and isolated using the method described for example 8, step 5 to afford (3R,4S)-3-amino-4-(3-boronopropyl)-1-(2-(piperidin-1-yl)ethyl)pyrrolidine-3-carboxylic acid (140 mg, 64%) as a glassy colorless solid. NMR (D2O) δ 3.85-4.05 (m, 2 H), 3.65-3.80 (m, 3 H), 3.35-3.55 (m, 5 H), 2.85-3.00 (m, 2 H), 2.60 (m, 1 H), 1.80-1.95 (m, 2 H), 1.55-1.75 (m, 4 H), 1.10-1.50 (m, 4 H), 0.63-0.73 (m, 2 H). MS (m+1): 328.3; MS (m−H2O+1): 310.0.

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