반응 #89574

반응 방정식

(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

수율 101.4%

용매

dichloromethane

반응 조건

후처리

1. 1
   workup.STIRRINGThe reaction mixture was stirred for another hour
2. 2
   기타it was quenched with 1N HCl (100 mL)
3. 3
   세척the organic phase was washed with saturated NaHCO3 and brine (500 mL)
4. 4
   건조The organic layers were dried over (MgSO4)
5. 5
   여과filtered
6. 6
   농축concentrated in vacua

실험 절차

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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