4-Methylmorpholine → (S)-N-((S)-6-Cyano-1,2,3,4-tetrahydroquinolin-3-yl)-2-hydroxy-2-phenylacetamide

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Reaction Steps

To a solution of 3-amino-1,2,3,4-tetrahydroquinoline-6-carbonitrile, dihydrochloride (10.03 g, 40.7 mmol), prepared as described in Example 1D, in DMF (100 mL) was added (S)-(+)-mandelic acid (7.45 g, 48.9 mmol), followed by EDAC (9.37 g, 48.9 mmol), HOBt (7.49 g, 48.9 mmol) and NMM (16.1 mL, 146.1 mmol). The reaction mixture was stirred at RT overnight, then diluted with EtOAc (200 mL), washed with water (50 mL×3), 1N aqueous HCl (50 mL), water (50 mL) and saturated aqueous NaCl, dried (Na2SO4) and concentrated. The residue was chromatographed (silica gel) eluting with EtOAc/hexanes (2:1 ratio), and the purified compound crystallized from acetone three times to give the title compound as the (S, S) diastereoisomer (2.54 g, 20% yield).

Provenance & Evidence