p-Xylyl bromide → (S)-3-((tert-Butyldimethylsilyl)oxy)-1-(4-methylbenzyl)pyrrolidin-2-one

HRID 1507262Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1507262
[Si:1]([O:8][C@H:9]1[CH2:13][CH2:12][NH:11][C:10]1=[O:14])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[H-].[Na+].Br[CH2:18][C:19]1[CH:24]=[CH:23][C:22]([CH3:25])=[CH:21][CH:20]=1>C1COCC1>[Si:1]([O:8][C@H:9]1[CH2:13][CH2:12][N:11]([CH2:18][C:19]2[CH:24]=[CH:23][C:22]([CH3:25])=[CH:21][CH:20]=2)[C:10]1=[O:14])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Komponenten

5

Edukt 3

HCID 7721p-Xylyl bromideHCID 24758Sodium hydrideHCID 10584804(S)-3-((tert-Butyldimethylsilyl)oxy)pyrrolidin-2-one

Produkt 1

HCID 123160669(S)-3-((tert-Butyldimethylsilyl)oxy)-1-(4-methylbenzyl)pyrrolidin-2-oneAusbeute 88 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

(S)-3-((tert-Butyldimethylsilyl)oxy)pyrrolidin-2-one (5 g, 23.22 mmol) was dissolved in anhydrous THF (46.4 ml) and the reaction mixture was cooled to 0° C. under a nitrogen atmosphere. Sodium hydride (1.393 g, 34.8 mmol) was then added in one portion and the reaction mixture was allowed to stir for 5 min before the dropwise addition of 1-(bromomethyl)-4-methylbenzene (5.37 g, 29 mmol) in anhydrous THF (46 ml). The reaction was allowed to stir at 0° C. for 5 min, then the cooling bath was removed and mixture was allowed to warm to rt overnight. The reaction was cautiously quenched with water (100 mL) and then extracted with ethyl acetate (3×100 mL). The combined organic layers were then washed with brine (200 mL) and dried (MgSO4). Evaporation of the solvent in vacuo gave the crude product (9.6 g, oil) which was then purified by silica gel chromatography (330 g of silica) eluting with a gradient of 0% to 20% ethyl acetate in hexanes to provide 6.53 g (88%) of the desired product. LC/MS (Conditions B) RT=4.320 min, (M+H)+=320.3; 1H NMR (400 MHz, chloroform-d) δ 7.15 (s, 4H), 4.42 (s, 2H), 4.37 (t, J=7.6 Hz, 1H), 3.32-3.18 (m, 1H), 3.10 (dt, J=9.7, 7.5 Hz, 1H), 2.36 (s, 3H), 2.29 (dtd, J=12.6, 7.6, 3.1 Hz, 1H), 1.97-1.84 (m, 1H), 0.95 (s, 9H), 0.20 (d, J=10.3 Hz, 6H).

Aufarbeitung

  1. customthe cooling bath was removed
  2. temperatureto warm to rt overnight
  3. customThe reaction was cautiously quenched with water (100 mL)
  4. extractionextracted with ethyl acetate (3×100 mL)
  5. washThe combined organic layers were then washed with brine (200 mL)
  6. dry with materialdried (MgSO4)
  7. customEvaporation of the solvent in vacuo
  8. customgave the crude product (9.6 g, oil) which
  9. customwas then purified by silica gel chromatography (330 g of silica)
  10. washeluting with a gradient of 0% to 20% ethyl acetate in hexanes

Quellen und Nachweise

ORD-Eintrag
ord-6d874cdf5c7e48c9bedc16a92d6913e6
Quelldatensatz
uspto-grants-2015_12
Patentnummer
US09221796B2

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