Diisobutylaluminum hydride → Ammonium Hydroxide

HRID 551093Notes

Reaction equation

HRID 551093 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[NH:14][C:13](=O)[C:6]3([CH3:16])[CH2:7][C:8](=[O:12])[NH:9][C:10]([CH:11]=1)=[C:5]23.CC(C[AlH]CC(C)C)C>C1COCC1.C1(C)C=CC=CC=1>[NH4+:9].[OH-:12].[F:1][C:2]1[CH:3]=[C:4]2[NH:14][CH2:13][C:6]3([CH3:16])[CH:7]=[CH:8][NH:9][C:10]([CH:11]=1)=[C:5]23

Participants

6

Reactant 2

HCID 14487Diisobutylaluminum hydrideHCID 67173014HCID 67173014, compound

Product 2

HCID 14923Ammonium HydroxideHCID 86629743HCID 86629743, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (±)-7-fluoro-2a-methyl-2a,5-dihydropyrrolo[4,3,2-de]quinoline-2,4(1H,3H)-dione from Step F (340 mg, 1.54 mmol) in THF (10 mL) at 0° C. was added DIBAL-H (7.72 mL of a 1 M solution in toluene, 7.72 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 washed with brine (20 mL), 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 the racemic title compound. The enantiomers were resolved by HPLC, utilizing a ChiralPak AD column and eluting with MeOH. The first major peak to elute was 7-fluoro-2a-methyl-1,2,2a,5-tetrahydropyrrolo[4,3,2-de]quinolin-4(3H)-one, enantiomer A, the title compound, and the second major peak to elute was 7-fluoro-2a-methyl-1,2,2a,5-tetrahydropyrrolo[4,3,2-de]quinolin-4(3H)-one, enantiomer B. MS: m/z=207 (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. washThe combined organic extracts were washed with brine (20 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by silica gel chromatography
  8. washeluting with a gradient of CH2Cl2

Sources & evidence

ORD record
ord-79942db720e74c4cb7d299be8935a1e7
Source dataset
uspto-grants-2011_05
Patent number
US07947677B2

Reaction notes

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