Hydrogen Peroxide → HCID 71140744, compound

HRID 629890Notes

Reaction equation

HRID 629890 reaction equation
[CH3:1][C:2]([CH3:31])([CH3:30])[CH2:3][N:4]1[C:12]2[C:7](=[N:8][C:9]([C:13]3[CH2:19][CH:18]4[N:20]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH:15]([CH2:16][CH2:17]4)[CH:14]=3)=[CH:10][CH:11]=2)[N:6]([CH3:28])[C:5]1=[O:29].[O:32]1CCCC1.B.OO.[OH-].[Na+]>CCOC(C)=O.C1COCC1>[CH3:1][C:2]([CH3:31])([CH3:30])[CH2:3][N:4]1[C:12]2[C:7](=[N:8][C:9]([CH:13]3[CH2:19][CH:18]4[N:20]([C:21]([O:23][C:24]([CH3:25])([CH3:27])[CH3:26])=[O:22])[CH:15]([CH2:16][CH2:17]4)[CH:14]3[OH:32])=[CH:10][CH:11]=2)[N:6]([CH3:28])[C:5]1=[O:29]

Participants

7

Reactant 4

HCID 784Hydrogen PeroxideHCID 14798Sodium HydroxideHCID 2723981Borane;tetrahydrofuranHCID 71135237HCID 71135237, compound

Product 1

HCID 71140744HCID 71140744, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a round bottom flask was added tert-butyl 3-[1-(2,2-dimethylpropyl)-3-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-5-yl]-8-azabicyclo[3.2.1]oct-2-ene-8-carboxylate (17-31) (1.5 g, 3.52 mmol), and anhydrous THF (15 mL). The reaction mixture was then cooled to 0° C. under an atmosphere of nitrogen, and added borane tetrahydrofuran COMPLEX (1M in THF) (3.87 ml, 3.87 mmol) dropwise over 10 minutes while stirring. Stirred for ˜10 minutes, then permitted to warm to room temperature for 30 minutes. Next cooled back to 0° C. and uncapped, and when open to atmosphere added hydrogen peroxide(35% by wt in H2O) (1.539 ml, 17.58 mmol) & sodium hydroxide (1M in H2O) (8.79 mL, 8.79 mmol) slowly over 20 minutes, then warmed to room temperature. The reaction was then permitted to stir overnight at room temperature (16 hours), then suspended in EtOAc, washed with a saturated solution of Na2S2O3, then saturated NaHCO3, followed by water and brine, dried over Na2SO4, filtered and concentrated. The resulting residue was purified by silica gel chromatography (0-100% EtOAc/Hex) to yield tert-Butyl 3-[1-(2,2-dimethylpropyl)-3-methyl-2-oxo-2,3-dihydro-1H-imidazo-[4,5-b]pyridin-5-yl]-2-hydroxy-8-azabicyclo[3.2.1]octane-8-carboxylate (20-1). HRMS (M+H)+: observed=429.2865, calculated=429.2860.

Workup

  1. stirringStirred for ˜10 minutes
  2. temperatureto warm to room temperature for 30 minutes
  3. temperatureNext cooled back to 0° C.
  4. temperaturewarmed to room temperature
  5. stirringto stir overnight at room temperature (16 hours)
  6. washwashed with a saturated solution of Na2S2O3
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe resulting residue was purified by silica gel chromatography (0-100% EtOAc/Hex)

Sources & evidence

ORD record
ord-6db0a8d24e644a408291784ae2e983ce
Source dataset
uspto-grants-2016_04
Patent number
US09315518B2

Reaction notes

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