Methanol → (2R,3R)-tert-butyl 2-((tert-butyldimethylsilyloxy)methyl)-3-(4-(trifluoromethyl)phenyl)aziridine-1-carboxylate

HRID 2075328

Reaktionsgleichung

Reaktionsgleichung von HRID 2075328
[H-].[Na+].CS(O[C@@H:8]([CH2:28][O:29][Si:30]([C:33]([CH3:36])([CH3:35])[CH3:34])([CH3:32])[CH3:31])[C@H:9]([NH:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[C:10]1[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][CH:11]=1)(=O)=O.CCOC(C)=O.CO>C1COCC1.CCCCCC>[Si:30]([O:29][CH2:28][C@H:8]1[C@@H:9]([C:10]2[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][CH:11]=2)[N:20]1[C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])([C:33]([CH3:36])([CH3:35])[CH3:34])([CH3:32])[CH3:31]

Komponenten

7

Edukt 4

HCID 887MethanolHCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 57634118(1R,2R)-1-((tert-Butoxycarbonyl)amino)-3-(tert-butyldimethylsilyloxy)-1-(4-(trifluoromethyl)phenyl)propan-2-yl methanesulfonate

Produkt 1

HCID 86613771(2R,3R)-tert-butyl 2-((tert-butyldimethylsilyloxy)methyl)-3-(4-(trifluoromethyl)phenyl)aziridine-1-carboxylateAusbeute 58,8 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittel2×HCID 8058HexaneLösungsmittel

Versuchsvorschrift

To a suspension of 4.0 g sodium hydride (60% dispersion in mineral oil) in 50 mL THF at 0° C. was added a solution (1R,2R)-1-((tert-butoxycarbonyl)amino)-3-(tert-butyldimethylsilyloxy)-1-(4-(trifluoromethyl)phenyl)-propan-2-yl methanesulfonate (13.5 g, 25.6 mmol) in 60 mL THF. The reaction progress was monitored by TLC (20% EtOAc in hexane). When no more starting material could be detected, 4 grams of MeOH was added to the mixture to remove the excess sodium hydride. The solvent was then removed at reduced pressure, and 200 mL of distilled water was added to the residue. The aqueous phase was extracted (3×150 mL) with EtOAc. The combined organic layers were washed with brine and dried over sodium sulfate. The crude product was then chromatographed eluting with 3% EtOAc in hexane. After removing the solvent, the product was obtained as a colorless oil (6.5 g, yield=58%). 1H NMR (400 MHz, CD3OD) o ppm 0.14-0.18 (m, 6 H) 0.95-0.98 (m, 9 H) 1.46 (s, 9 H) 2.78 (q, J=2.80 Hz, 1H) 3.64 (d, J=2.93 Hz, 1H) 4.11 (ddd, J=18.19, 11.93, 2.54 Hz, 2H) 7.48 (d, J=8.22 Hz, 2H) 7.66 (d, J=8.02 Hz, 2H).

Aufarbeitung

  1. customto remove the excess sodium hydride
  2. customThe solvent was then removed at reduced pressure, and 200 mL of distilled water
  3. additionwas added to the residue
  4. extractionThe aqueous phase was extracted (3×150 mL) with EtOAc
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over sodium sulfate
  7. customThe crude product was then chromatographed
  8. washeluting with 3% EtOAc in hexane
  9. customAfter removing the solvent

Quellen und Nachweise

ORD-Eintrag
ord-675c53f1086c448389eee92aba00941e
Quelldatensatz
uspto-grants-2011_04
Patentnummer
US07919504B2

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