Diisobutylaluminum hydride → Ammonium Hydroxide

HRID 2426241Notes

Reaction equation

HRID 2426241 reaction equation
[O:1]=[C:2]1[C:6]2([CH2:15][NH:16][C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])[CH2:7][C:8](=O)[NH:9][C:10]3[CH:11]=[CH:12][CH:13]=[C:4]([C:5]=32)[NH:3]1.CC(C[AlH]CC(C)C)C>C1COCC1.C1(C)C=CC=CC=1>[NH4+:3].[OH-:1].[C:19]([O:18][C:17](=[O:23])[NH:16][CH2:15][C:6]12[C:2](=[O:1])[NH:3][C:4]3[C:5]1=[C:10]([CH:11]=[CH:12][CH:13]=3)[NH:9][CH2:8][CH2:7]2)([CH3:22])([CH3:20])[CH3:21]

Participants

6

Reactant 2

HCID 14487Diisobutylaluminum hydrideHCID 86629739HCID 86629739, compound

Product 2

HCID 14923Ammonium HydroxideHCID 57663766HCID 57663766, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (±)-tert-butyl (2,4-dioxo-1,2,4,5-tetrahydropyrrolo[4,3,2-de]quinolin-2a(3H)-yl)methylcarbamate from Step C (1.20 g, 3.78 mmol) in THF (20 mL) at 0° C. was added DIBAL-H (18.9 mL of a 1 M solution in toluene, 18.9 mmol). The reaction mixture was stirred for 2 h and then quenched by the slow addition of saturated aqueous sodium potassium tartrate (100 mL) and extracted with EtOAc (3×50 mL). The combined organic extracts were dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by silica gel chromatography, eluting with a gradient of CH2Cl2:MeOH:NH4OH—100:0:0 to 95:5:1, to give (±)-tert-butyl[(2-oxo-1,2,4,5-tetrahydropyrrolo[4,3,2-de]quinolin-2a(3H)-yl)methyl]carbamate, which eluted first, and the racemic title compound, which eluted second. The enantiomers were resolved by HPLC, utilizing a ChiralPak AD column and eluting with hexane:EtOH:Et2NH—60:40:0.1. The first major peak to elute was tert-butyl [(4-oxo-1,2,4,5-tetrahydropyrrolo[4,3,2-de]quinolin-2a(3H)-yl)methyl]carbamate, enantiomer A, the title compound, and the second major peak to elute was tert-butyl[(4-oxo-1,2,4,5-tetrahydropyrrolo[4,3,2-de]quinolin-2a(3H)-yl)methyl]carbamate, enantiomer B. MS: m/z=304 (M+1).

Workup

  1. customquenched by the slow addition of saturated aqueous sodium potassium tartrate (100 mL)
  2. extractionextracted with EtOAc (3×50 mL)
  3. dry with materialThe combined organic extracts were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by silica gel chromatography
  7. washeluting with a gradient of CH2Cl2

Sources & evidence

ORD record
ord-822ea374f3fd4227977a14f414a0c721
Source dataset
uspto-grants-2011_06
Patent number
US07968540B2

Reaction notes

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