Diisobutylaluminum hydride → HCID 58318598, compound

HRID 473419Notes

Reaction equation

HRID 473419 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][N:10]=2)[N:5]=[C:4]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=2)[C:3]=1[C:19](OCC)=[O:20].CC(C[AlH]CC(C)C)C.[H-].[Al+3].[Li+].[H-].[H-].[H-]>C1(C)C=CC=CC=1>[F:18][C:14]1[CH:13]=[C:12]([C:4]2[C:3]([CH2:19][OH:20])=[CH:2][C:11]3[C:6](=[CH:7][CH:8]=[CH:9][N:10]=3)[N:5]=2)[CH:17]=[CH:16][CH:15]=1

Participants

5

Reactant 3

HCID 14487Diisobutylaluminum hydride2×HCID 21226445Aluminium lithium hydrideHCID 67240006HCID 67240006, compound

Product 1

HCID 58318598HCID 58318598, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a stirred solution of ethyl 4-chloro-2-(3-fluorophenyl)-1,5-naphthyridine-3-carboxylate (614 mg, 1.856 mmol) in toluene (10 mL) at 0° C. was added DIBAL-H (4.1 mL, 4.1 mmol) dropwise over 2 min. After this time the reaction was allowed to warm to rt for 1 h. After this time more DIBAL-H (4.1 mL, 4.1 mmol) was added and the reaction was stirred at rt overnight. After this time lithium aluminium hydride (0.92 mL, 3.68 mmol, 4.0M solution in THF) was added and the reaction was stirred at rt for 10 min. After this time the reaction was carefully quenched with water (8 mL), NaOH (5 mL, 1.0M aq. solution) and water (5 mL). To the stirred mixture was added EtOAc (50 mL) and Rochelle's salt (50 mL, satd aq. solution) and the mixture was stirred at rt for 2 h. After this time the separated organic layer was washed with water, dried over MgSO4, filtered and concentrated in vacuo. The resulting solid was purified by column chromatography on silica gel using a gradient from 1:0 to 1:2 of hexane:EtOAc to give (2-(3-fluorophenyl)-1,5-naphthyridin-3-yl)methanol: LC-MS (ESI) m/z 255.1 [M+H]+.

Workup

  1. stirringthe reaction was stirred at rt for 10 min
  2. customAfter this time the reaction was carefully quenched with water (8 mL), NaOH (5 mL, 1.0M aq. solution) and water (5 mL)
  3. additionTo the stirred mixture was added EtOAc (50 mL) and Rochelle's salt (50 mL, satd aq. solution)
  4. stirringthe mixture was stirred at rt for 2 h
  5. washAfter this time the separated organic layer was washed with water
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe resulting solid was purified by column chromatography on silica gel using a gradient from 1:0 to 1:2 of hexane

Sources & evidence

ORD record
ord-f2d349ba7d014a8fb39e154deacc002a
Source dataset
uspto-grants-2014_01
Patent number
US08633313B2

Reaction notes

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