Sodium t-butoxide → 2-[5-((2S,3'S)-2-Methyl-[1,3']bipyrrolidinyl-1'-yl)-pyridin-2-yl]-8-oxa-2-aza-spiro[4.5]decan-1-one

HRID 2401136Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2401136
Br[C:2]1[CH:3]=[CH:4][C:5]([N:8]2[CH2:12][CH2:11][C:10]3([CH2:17][CH2:16][O:15][CH2:14][CH2:13]3)[C:9]2=[O:18])=[N:6][CH:7]=1.[CH3:19][C@H:20]1[CH2:24][CH2:23][CH2:22][N:21]1[C@H:25]1[CH2:29][CH2:28][NH:27][CH2:26]1.CC(C)([O-])C.[Na+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(C)C=CC=CC=1>[CH3:19][C@H:20]1[CH2:24][CH2:23][CH2:22][N:21]1[C@H:25]1[CH2:29][CH2:28][N:27]([C:2]2[CH:3]=[CH:4][C:5]([N:8]3[CH2:12][CH2:11][C:10]4([CH2:17][CH2:16][O:15][CH2:14][CH2:13]4)[C:9]3=[O:18])=[N:6][CH:7]=2)[CH2:26]1

Komponenten

6

Edukt 3

HCID 23676156Sodium t-butoxideHCID 59401808(2S,3'S)-2-Methyl-[1,3]bipyrrolidinylHCID 674786592-(5-Bromo-pyridin-2-yl)-8-oxa-2-aza-spiro[4.5]decan-1-one

Produkt 1

HCID 545911532-[5-((2S,3'S)-2-Methyl-[1,3']bipyrrolidinyl-1'-yl)-pyridin-2-yl]-8-oxa-2-aza-spiro[4.5]decan-1-one

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

A mixture of 2-(5-bromo-pyridin-2-yl)-8-oxa-2-aza-spiro[4.5]decan-1-one (0.05 g, 0.161 mmol), (2S,3′S)-2-Methyl-[1,3′]bipyrrolidinyl (0.037 g, 0.242 mmol), (−)R-BINAP (0.006 g, 0.01 mmol), and anhydrous toluene (3 mL) was de-gassed and refilled with N2 in three cycles. Pd2(dba)3 (0.003 g, 0.0032 mmol,), and sodium t-butoxide (0.023 g, 0.242 mmol) was then added to the mixture and de-gassed and refilled with N2 in three additional cycles. The reaction mixture was heated and stirred at 90° C. for 16 hours. The reaction mixture was allowed to cool to room temperature and quenched with water (1 mL). The aqueous phase was extracted with dichloromethane (3×10 mL). The combined organics were washed with sodium bicarbonate (5 mL), and brine (10 mL), dried over Na2SO4, concentrated under vacuum. Purification by column chromatography on silica gel (0-10%) methanol in dichloromethane afforded 0.0349 (56%) of the title compound.

Aufarbeitung

  1. customwas de-gassed
  2. additionrefilled with N2 in three cycles
  3. customde-gassed
  4. additionrefilled with N2 in three additional cycles
  5. temperatureThe reaction mixture was heated
  6. temperatureto cool to room temperature
  7. customquenched with water (1 mL)
  8. extractionThe aqueous phase was extracted with dichloromethane (3×10 mL)
  9. washThe combined organics were washed with sodium bicarbonate (5 mL), and brine (10 mL)
  10. dry with materialdried over Na2SO4
  11. concentrationconcentrated under vacuum
  12. customPurification by column chromatography on silica gel (0-10%) methanol in dichloromethane

Quellen und Nachweise

ORD-Eintrag
ord-f793915dd07542f1a41ebd6e0395fd34
Quelldatensatz
uspto-grants-2014_08
Patentnummer
US08796278B2

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