2-Ethoxy-1-(ethoxycarbonyl)-1,2-dihydroquinoline → 3-t-Butoxycarbonylamino-3-methyl-N-benzyl-N-[2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3-(R)-yl]-butanamide

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Reaction Steps

A solution of 90 mg (0.34 mmol) of 3(R)-(benzylamino)-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one in 1.5 mL of tetrahydrofuran under nitrogen at room temperature was treated with 73 mg (0.34 mmol, 1 eq.) of 3-t-butoxycarbonylamino-3-methylbutanoic acid (Example 31, Step E) followed by 94 mg (0.38 mmol, 1.1 eq.) of 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline (EEDQ). Most of the solvent was evaporated under a stream of nitrogen and the resulting reaction mixture (thick syrup approx. 0.3 mL) was stirred for 3 days. The mixture was evaporated to dryness under vacuum and the residue purified by medium pressure liquid chromatography on silica, eluting with ethyl acetate/hexane (1:1) to afford 45 mg (mmol, 33%) of product. 1H NMR (200MHz, CDCl3): 1.28 (s,3H), 1.32 (s,3H), 1.35 (s,9H), 2.16 (m,2H), 2.35 (d,14Hz,1H), 2.58 (d,14Hz,1H), 2.60 (m,1H), 2.81 (m,1H), 4.70 (d,18Hz,1H), 4.99 (d,18Hz,1H), 5.37 (t,10Hz,1H), 5.83 (br s,1H), 6.98 (d,7Hz,1H), 7.05-7.45 (m,5H), 7.50-7.85 (m,3H), 8.13 (t,8Hz,1H), 8.90 (m,1H). FAB-MS: calculated for C27H35N3O4 465; found 466 (M+H)48%).

Provenance & Evidence