Benzyl Bromide → 4-(R)-[1-(S)-benzyloxy-3-(3-benzyloxyphenyl)-2-(S)-dibenzylaminopropyl]-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl ester

HRID 20349

Reaktionsgleichung

Reaktionsgleichung von HRID 20349
[C:1]([O:5][C:6]([N:8]1[C@@H:12]([C@@H:13]([OH:24])[C@@H:14]([NH2:23])[CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([OH:22])[CH:17]=2)[CH2:11][O:10][C:9]1([CH3:26])[CH3:25])=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH2:29](Br)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1>CCCCCCCC[N+](CCCCCCCC)(CCCCCCCC)C.[Cl-].[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.O1CCCC1.C(OCC)(=O)C>[C:1]([O:5][C:6]([N:8]1[C@@H:12]([C@@H:13]([O:24][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C@@H:14]([N:23]([CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([O:22][CH2:29][C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[CH:17]=2)[CH2:11][O:10][C:9]1([CH3:26])[CH3:25])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Komponenten

8

Edukt 3

HCID 7498Benzyl Bromide2×HCID 24758Sodium hydride2×HCID 685597324-(R)-[2-(S)-Amino-1-(S)-hydroxy-3-(3-hydroxyphenyl)-propyl]-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl ester

Produkt 1

HCID 685579764-(R)-[1-(S)-benzyloxy-3-(3-benzyloxyphenyl)-2-(S)-dibenzylaminopropyl]-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl ester

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 21218Trioctylmethylammonium chlorideKatalysatorHCID 74236Tetrabutylammonium BromideKatalysatorHCID 8028TetrahydrofuranLösungsmittel2×HCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

Add tricaprylmethylammonium chloride (Aliquat® 336) (4.5 g, 11.2 mmol) and tetrabutylammonium bromide (TBAB) (5.7 g, 15.7 mmol) to a solution of 4-(R)-[2-(S)-amino-1-(S)-hydroxy-3-(3-hydroxyphenyl)-propyl]-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl ester (16.45 g, crude) in tetrahydrofuran (200 mL). Add portionwise 95% sodium hydride (2.6 g, 90 mmol) and stir for 10 minutes. Add benzyl bromide (13.4 mL, 112.5 mmol) and heat at 60° C. for 40 minutes and concentrate. Add more 95% sodium hydride (5.4 g, 225 mmol) and benzyl bromide (27 mL, 225 mmol) in tetrahydrofuran (−5 mL) and stir overnight at 65° C. Dilute with ethyl acetate, quench with water (300 mL), wash with water, and saturated aqueous sodium chloride. Extract the aqueous washes with ethyl acetate, comvine the organic layers, dry (magnesium sulfate), filter and purify twice (silica gel chromatography, eluting with 5:95 to 10:90 ethyl acetate:hexanes) to give the desired compound as an orange residue (16.01 g, 49%).

Aufarbeitung

  1. concentrationconcentrate
  2. stirringstir overnight at 65° C
  3. customquench with water (300 mL)
  4. washwash with water, and saturated aqueous sodium chloride
  5. extractionExtract the aqueous washes with ethyl acetate
  6. dry with materialdry (magnesium sulfate)
  7. filtrationfilter
  8. custompurify twice
  9. wash(silica gel chromatography, eluting with 5:95 to 10:90 ethyl acetate:hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-90f47e08bb984cd5a0e1a8455c23aa0d
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07745438B2

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