Binap, (A+-)- → (3R,4S)-3-amino-4-(3-boronopropyl)-1-(4-methylpyridin-3-yl)pyrrolidine-3-carboxylic acid

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Reaction Conditions

Reaction Steps

A stirred solution of (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 3-bromo-4-methylpyridine (0.258 g, 1.5 mmol) in anhydrous toluene (5 mL) was degassed under nitrogen for 15 min, then treated with Pd2dba3 (46 mg, 0.05 mmol), rac-binap (50 mg, 0.075 mmol), and sodium t-butoxide (0.18 g, 1.87 mmol). The mixture was heated to 70° C. for 18 h, cooled to room temperature, diluted with methylene chloride (20 mL), filtered through Celite® and the filtrate concentrated. the crude material was deprotected and isolated using the method described for example 8, step 5 to afford (3R,4S)-3-amino-4-(3-boronopropyl)-1-(4-methylpyridin-3-yl)pyrrolidine-3-carboxylic acid (22 mg, 12%) as a pale amber solid. NMR (D2O) δ 7.99 (d, J=6 Hz, 1 H), 7.95 (s, 1 H), 7.57 (d, J=6 Hz, 1 H), 3.80 (d, J=5 Hz, 2 H), 3.72 (t, J=9.5 Hz, 1 H), 3.25 (t, J=9.5 Hz, 1 H), 2.49 (s, 3 H), 2.40-2.60 (m, 1 H), 1.50-1.60 (m, 1 H), 1.20-1.45 (m, 3 H), 0.65-0.75 (m, 2 H). MS (m−H2O+1): 290.0; MS (m−2 H2O+1): 271.9.

Provenance & Evidence