Sodium t-butoxide → HCID 54591154, compound

HRID 2401137Notes

Reaction equation

HRID 2401137 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:25][CH2:24][C:11]2([C:15](=[O:16])[N:14]([C:17]3[CH:22]=[N:21][C:20](Br)=[CH:19][N:18]=3)[CH2:13][CH2:12]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:26][C@H:27]1[CH2:31][CH2:30][CH2:29][N:28]1[C@H:32]1[CH2:36][CH2:35][NH:34][CH2:33]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>[C:1]([O:5][C:6]([N:8]1[CH2:25][CH2:24][C:11]2([C:15](=[O:16])[N:14]([C:17]3[CH:22]=[N:21][C:20]([N:34]4[CH2:35][CH2:36][C@H:32]([N:28]5[CH2:29][CH2:30][CH2:31][C@@H:27]5[CH3:26])[CH2:33]4)=[CH:19][N:18]=3)[CH2:13][CH2:12]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 23676156Sodium t-butoxideHCID 59401808(2S,3'S)-2-Methyl-[1,3]bipyrrolidinylHCID 86677567HCID 86677567, compound

Product 1

HCID 54591154HCID 54591154, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 2-(5-bromo-pyrazin-2-yl)-1-oxo-2,8-diaza-spiro[4.5]decane-8-carboxylic acid tert-butyl ester (0.06 g, 0.146 mmol), (2S,3′S)-2-methyl-[1,3′]bipyrrolidinyl (0.045 g, 0.292 mmol), R-(−)-BINAP (0.007 g, 0.011 mmol), and anhydrous toluene (3 mL) was de-gassed and refilled with N2 in three cycles. Pd2(dba)3 (0.0034 g, 0.0037 mmol,), and sodium t-butoxide (0.021 g, 0.212 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 0.0257 (37%) of the title compound.

Workup

  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

Sources & evidence

ORD record
ord-09ac48223f034801b59a0b17c074fd6f
Source dataset
uspto-grants-2014_08
Patent number
US08796278B2

Reaction notes

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