Diisobutylaluminum hydride → Diisopropyl Ether

HRID 2243353Notes

Reaction equation

HRID 2243353 reaction equation
[NH:1]1[C:5]2[N:6]=[CH:7][CH:8]=[C:9]([C:10]([NH:12][CH:13]3[C:25]4[CH:24]=[CH:23][CH:22]=[C:21]([C:26]([OH:28])=[O:27])[C:20]=4[C:19]4[C:14]3=[CH:15][CH:16]=[CH:17][CH:18]=4)=[O:11])[C:4]=2[CH:3]=[CH:2]1.[H-].[CH:30]([Al+]C(C)C)([CH3:32])[CH3:31].[CH3:37]C(C[AlH]CC(C)C)C>O1CCCC1.C1(C)C=CC=CC=1>[CH:30]([O:28][CH:26]([CH3:21])[CH3:37])([CH3:32])[CH3:31].[NH:1]1[C:5]2[N:6]=[CH:7][CH:8]=[C:9]([C:10]([NH:12][CH:13]3[C:25]4[CH:24]=[CH:23][CH:22]=[C:21]([CH2:26][OH:27])[C:20]=4[C:19]4[C:14]3=[CH:15][CH:16]=[CH:17][CH:18]=4)=[O:11])[C:4]=2[CH:3]=[CH:2]1

Participants

7

Reactant 3

HCID 14487Diisobutylaluminum hydrideHCID 21896610Diisopropylaluminium hydrideHCID 68689319HCID 68689319, compound

Product 2

HCID 7914Diisopropyl EtherHCID 67358848HCID 67358848, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

In a 100 ml three-necked flask under argon, reflux a suspension of 1 g of methyl ester of 9(R,S)-[(1H-pyrrolo[2,3-b]pyridine-4-carbonyl)amino]-9H-fluorene-4-carboxylic acid, obtained in the previous stage, in 50 ml of anhydrous tetrahydrofuran, and then add, dropwise, 7.825 ml of a 20% solution of diisopropylaluminium hydride (DIBAL-H) in toluene. After stirring for 15 minutes at reflux, add a further 2.6 ml of the above solution of DIBAL-H and maintain the reflux for a further 15 minutes. After cooling to room temperature, the reaction medium is run, dropwise, into 25 ml of a saturated aqueous solution of ammonium chloride, and then extracted 3 times with 25 ml of ethyl acetate. The combined organic phases are dried over magnesium sulphate and concentrated to dryness under reduced pressure. After purification by flash chromatography on silica gel (40-63 μm), eluting with a mixture of dichloromethane and methanol (97.5/2.5 by volume), and then formation of a paste with diisopropyl ether, in this way we obtain 200 mg of 9(R,S)-[(1H-pyrrolo[2,3-b]pyridine-4-carbonyl)amino]-9H -fluorene-4-methanol, in the form of a beige solid, which is used, with the following characteristics:

Workup

  1. temperatureIn a 100 ml three-necked flask under argon, reflux
  2. additionadd
  3. temperatureat reflux
  4. temperaturemaintain the
  5. temperaturereflux for a further 15 minutes
  6. extractiondropwise, into 25 ml of a saturated aqueous solution of ammonium chloride, and then extracted 3 times with 25 ml of ethyl acetate
  7. dry with materialThe combined organic phases are dried over magnesium sulphate
  8. concentrationconcentrated to dryness under reduced pressure
  9. customAfter purification by flash chromatography on silica gel (40-63 μm)
  10. washeluting with a mixture of dichloromethane and methanol (97.5/2.5 by volume)

Sources & evidence

ORD record
ord-b3f6734996b5439782e631978ec03028
Source dataset
uspto-grants-2010_03
Patent number
US07674795B2

Reaction notes

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