Reaktion #89574

Reaktionsgleichung

(S)-2-tert-butoxycarbonylamino-3-phenyl-propionic acid

N-methylmorpholine

triethylamine

isobutyl chloroformate

N,O-dimethylhydroxylamine hydrochloride

→

[(S)-1-(methoxy-methyl-carbamoyl)-2-phenyl-ethyl]-carbamic acid tert-butyl ester

Ausbeute 101.4%

Lösungsmittel

dichloromethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGThe reaction mixture was stirred for another hour
2. 2
   Sonstigeit was quenched with 1N HCl (100 mL)
3. 3
   Waschenthe organic phase was washed with saturated NaHCO3 and brine (500 mL)
4. 4
   TrocknenThe organic layers were dried over (MgSO4)
5. 5
   Filtrationfiltered
6. 6
   Einengenconcentrated in vacua

Vorschrift

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).

Quelle