Sodium hydride → 4-(6-Chloro-2-oxo-2H-chromen-4-ylamino)-3,3-dimethyl-piperidine-1-carboxylic acid ethyl ester

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Reaction Steps

To a solution of the 4-amino-3,3-dimethyl-piperidine-1-carboxylic acid ethyl ester (131 mg, 0.654 mmol) in DMF was added NaH (36.4 mg, 0.910 mmol) under nitrogen, and the mixture was stirred 10 min before trifluoro-methanesulfonic acid 6-chloro-2-oxo-2H-chromen-4-yl ester (prepared as before, 184 mg, 0.519 mmol) in DMF was added slowly, dropwise. The mixture was stirred 3 d before being concentrated with nitrogen flow to about half its original volume. The mixture was partitioned between EtOAc and H2O and the layers were separated. The aqueous was extracted with EtOAc (3×) and the combined organics were washed with H2O, saturated aqueous NaCl, dried over MgSO4, filtered, and concentrated in vacuo. Silica gel chromatography eluting with a gradient of 0 to 5% MeOH in CH2Cl2 afforded 119 mg (56%) of the title compound as a yellow solid. MS (ESI(+)Q1MS) m/z 379 (M+H)+; 1H NMR (300 MHz, DMSO) δ ppm 0.83-0.93 (m, 6H), 1.19 (t, 3H, J=7.0 Hz), 1.50-1.63 (m, 1H), 1.70-1.91 (m, 1H), 2.67-3.07 (m, 2H), 3.58-3.84 (m, 2H), 3.92-4.14 (m, 3H), 5.55 (s, 1H), 6.77-6.88 (m, 1H), 7.30-7.40 (m, 1H), 7.60-7.69 (m, 1H), 8.40-8.48 (m, 1H).

Provenance & Evidence