(-)-Epichlorohydrin → ((2S,5S)-4-Benzyl-5-(((tert-butyldimethylsilyl)oxy)methyl)morpholin-2-YL)methanol

HRID 629694Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 629694
[CH2:1]([NH:8][C@H:9]([CH2:12][O:13][Si:14]([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15])[CH2:10][OH:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:21]([C@@H:23]1[O:25][CH2:24]1)Cl.Cl([O-])(=O)(=O)=O.[Li+].C[O-].[Na+]>C1(C)C=CC=CC=1.CO.[NH4+].[Cl-]>[CH2:1]([N:8]1[C@H:9]([CH2:12][O:13][Si:14]([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:15])[CH3:16])[CH2:10][O:11][C@H:23]([CH2:24][OH:25])[CH2:21]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Komponenten

8

Edukt 4

HCID 2734062(-)-EpichlorohydrinHCID 10942334Sodium Methoxide2×HCID 11770896(2S)-2-(benzylamino)-3-{[tert-butyl(dimethyl)silyl]oxy}propan-1-olHCID 23665649Lithium perchlorate

Produkt 1

HCID 86726300((2S,5S)-4-Benzyl-5-(((tert-butyldimethylsilyl)oxy)methyl)morpholin-2-YL)methanol

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 887MethanolLösungsmittel3×HCID 1140TolueneLösungsmittel2×HCID 25517Ammonium ChlorideLösungsmittel

Versuchsvorschrift

To (2S)-2-(benzylamino)-3-{[tert-butyl(dimethyl)silyl]oxy}propan-1-ol (1 eq) in Toluene (0.3 M) at rt was added (R)-(−)-epichlorohydrin (1.3 eq.) and Lithium perchlorate (1.3 eq) was then slowly added over 2 hours. The mixture was stirred at rt for 48 hrs and sodium methoxide (2.5 eq of a 25% solution of NaOMe in MeOH) was added. MeOH was then added to the reaction mixture to obtain a 4:1 ratio of toluene:MeOH as solvent. The reaction mixture was stirred for 48 hrs at rt and diluted with saturated aqueous NH4Cl. The aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated. The crude product was purified by automated SiO2 flash chromatography system using solvent gradient of 0% EtOAc/Hex to 25% EtOAc/Hex to afford the desired compound.

Aufarbeitung

  1. additionwas then slowly added over 2 hours
  2. stirringThe reaction mixture was stirred for 48 hrs at rt
  3. extractionThe aqueous layer was extracted with EtOAc
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified by automated SiO2 flash chromatography system

Quellen und Nachweise

ORD-Eintrag
ord-874dedb56d9345328271d55a042551a6
Quelldatensatz
uspto-grants-2016_04
Patentnummer
US09315475B2

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