Diisobutylaluminum hydride → HCID 86732807, compound

HRID 525938Notes

Reaction equation

HRID 525938 reaction equation
[CH2:1]([N:3]1[C:12]2[C:7](=[C:8]([F:33])[C:9]([O:23][CH2:24][C:25]3[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=3)=[C:10]([O:13][CH2:14][C:15]3[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=3)[CH:11]=2)[C:6](=[O:34])[C:5]([C:35](O)=[O:36])=[CH:4]1)[CH3:2].ClC(OCC(C)C)=O.CC(C[AlH]CC(C)C)C>O1CCCC1.C1(C)C=CC=CC=1>[CH2:1]([N:3]1[C:12]2[C:7](=[C:8]([F:33])[C:9]([O:23][CH2:24][C:25]3[CH:26]=[CH:27][C:28]([O:31][CH3:32])=[CH:29][CH:30]=3)=[C:10]([O:13][CH2:14][C:15]3[CH:16]=[CH:17][C:18]([O:21][CH3:22])=[CH:19][CH:20]=3)[CH:11]=2)[C:6](=[O:34])[C:5]([CH2:35][OH:36])=[CH:4]1)[CH3:2]

Participants

6

Reactant 3

HCID 14487Diisobutylaluminum hydrideHCID 62365Isobutyl chloroformateHCID 86732805HCID 86732805, compound

Product 1

HCID 86732807HCID 86732807, compoundYield 59.1%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of 1-ethyl-5-fluoro-6,7-bis((4-methoxybenzyl)oxy)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (20 g, 39.4 mmol) in Tetrahydrofuran (THF) (100 mL) was added TEA (6.04 mL, 43.3 mmol) and isobutyl chloroformate (5.69 mL, 43.3 mmol). The resulting mixture was stirred at r.t. for 1 h. Then the mixture was cooled down to −78° C. and a solution of DIBAL-H (52.5 mL, 79 mmol) in toluene (1.5 M) was added. The mixture was stirred at the same temperature for 2 h, LCMS indicated completion of the reaction. The reaction was quenched with sat. NH4Cl (aq.), and was warmed up to r.t., concentrated, diluted with sat. NH4Cl and extracted with dichloromethane. The organic mixture was filtered through Celite to remove gummy precipitate. The combined organic solution was then washed with brine, dried over sodium sulfate, filtered and the filtrate was concentrated in vacuo to afford 1-ethyl-5-fluoro-3-(hydroxymethyl)-6,7-bis((4-methoxybenzyl)oxy)quinolin-4(1H)-one (11.5 g, 23.30 mmol, 59.1% yield) as a yellow solid, which was used in the next oxidation step without further purification. LCMS: (M+H)+: 494.2

Workup

  1. temperatureThen the mixture was cooled down to −78° C.
  2. stirringThe mixture was stirred at the same temperature for 2 h
  3. customcompletion of the reaction
  4. customThe reaction was quenched with sat. NH4Cl (aq.)
  5. temperaturewas warmed up to r.t.
  6. concentrationconcentrated
  7. additiondiluted with sat. NH4Cl
  8. extractionextracted with dichloromethane
  9. filtrationThe organic mixture was filtered through Celite
  10. customto remove gummy precipitate
  11. washThe combined organic solution was then washed with brine
  12. dry with materialdried over sodium sulfate
  13. filtrationfiltered
  14. concentrationthe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-a2a76a9947054169b1d17296bcb3eae8
Source dataset
uspto-grants-2016_05
Patent number
US09340556B2

Reaction notes

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