4-Methylmorpholine → 1,1-Dimethylethyl N-((1S)-2-(methoxymethylamino)-2-oxo-1-(phenylmethyl)ethyl)carbamate

Beteiligte Stoffe

Reaktionsschritte

To a solution of (S)-2-tert-butoxycarbonylamino-3-phenyl-propionic acid (24.85 g, 93.66 mmol) in dichloromethane (150 mL) was added N-methylmorpholine (10.3 mL, 93.66 mmol), followed by addition of isobutyl chloroformate (12.25 mL, 93.66 mmol) at 0° C. The reaction mixture was stirred for 20 min. then N,O-dimethylhydroxylamine hydrochloride (9.14 g, 93.66 mmol) in one portion was added. Subsequently, triethylamine (13 mL, 93.66 mmol) was added dropwise over 15 min. The reaction mixture was stirred for another hour, then it was quenched with 1N HCl (100 mL) and the organic phase was washed with saturated NaHCO3 and brine (500 mL). The organic layers were dried over (MgSO4), filtered, and concentrated in vacua to give the Weinreb amide of Formula VII(a), [(S)-1-(methoxy-methyl-carbamoyl)-2-phenyl-ethyl]-carbamic acid tert-butyl ester as a clear sticky oil (29.3 g, 100%). 1H NMR (400 MHz, d6-DMSO): δ (ppm) 7.33-7.09 (m, 6H), 4.61-4.47 (m, 1H), 3.70 (s, 3H), 3.08 (s, 3H), 2.89-2.78 (m, 1H), 2.75-2.63 (m, 1H), 1.29 (s, 9H).

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