4-Methylmorpholine → (R)-(+)-3-Benzyloxy-2-(Boc-amino)-1-propanol

HRID 339480

Reaktionsgleichung

[CH2:1]([O:8][CH2:9][C@H:10]([NH:14][C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[C:11](O)=[O:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN1CCOCC1.ClC(OCC(C)C)=O.[BH4-].[Na+]>COCCOC>[CH2:1]([O:8][CH2:9][C@H:10]([NH:14][C:15](=[O:16])[O:17][C:18]([CH3:20])([CH3:19])[CH3:21])[CH2:11][OH:12])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Komponenten

Reaktionsbedingungen

Temperatur: -20 °C

Versuchsvorschrift

(2S)-3-(benzyloxy)-2-[(tert-butoxycarbonyl)amino]propanoic acid (7.2 g, 24.4 mmole) was dissolved in ethylene glycol dimethyl ether (50 mL). N-Methylmorpholine (2.7 ml, 24.4 mmole) was added, and the resulting clear solution was cooled to −20° C. Isobutyl chloroformate (3.19 ml, 24.4 mmole) was added dropwise to cause N-methylmorpholine HCl salt precipitation. Stirring was continued for 15 min and the supernatant was then transferred via a filter-tipped funnel into a rapidly stirred solution of NaBH4 (2.93 g, 73.2 mmole) in ice water and washed with dry DME. After the mixture was stirred for 30 min, it was extracted with EtOAc and washed with H2O. The organic layers were combined, dried over Na2SO4, and concentrated in vacuo. Purification by chromatography (silica, 4/1: Hexane/EtOAc, Rf=0.2) afforded tert-butyl N-[(1R)-2-(benzyloxy)-1-(hydroxymethyl)ethyl]carbamate as a white solid (6.3 g, 92%).

Aufarbeitung

customN-methylmorpholine HCl salt precipitation
washwashed with dry DME
stirringAfter the mixture was stirred for 30 min
extractionit was extracted with EtOAc
washwashed with H2O
dry with materialdried over Na2SO4
concentrationconcentrated in vacuo
customPurification by chromatography (silica, 4/1: Hexane/EtOAc, Rf=0.2)

Quellen und Nachweise

ORD-Eintrag: ord-d14da13e9cb94b56a27abd58aeadfe2b
Quelldatensatz: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patentnummer: US08895497B2

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