Diisobutylaluminum hydride → HCID 86732818, compound

HRID 525950Notes

Reaction equation

HRID 525950 reaction equation
[CH2:1]([N:3]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([O:23][CH2:24][C:25]3[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=3)[C:11]=2[O:13][CH2:14][C:15]2[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=2)[C:6](=[O:33])[C:5]([C:34](O)=[O:35])=[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](=[CH:8][CH:9]=[C:10]([O:23][CH2:24][C:25]3[CH:26]=[CH:27][C:28]([O:31][CH3:32])=[CH:29][CH:30]=3)[C:11]=2[O:13][CH2:14][C:15]2[CH:16]=[CH:17][C:18]([O:21][CH3:22])=[CH:19][CH:20]=2)[C:6](=[O:33])[C:5]([CH2:34][OH:35])=[CH:4]1)[CH3:2]

Participants

6

Reactant 3

HCID 14487Diisobutylaluminum hydrideHCID 62365Isobutyl chloroformateHCID 86732819HCID 86732819, compound

Product 1

HCID 86732818HCID 86732818, compoundYield 52.4%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of 1-ethyl-7,8-bis((4-methoxybenzyl)oxy)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (22 g, 44.9 mmol) in Tetrahydrofuran (THF) (300 mL) was added TEA (6.89 mL, 49.4 mmol) and isobutyl chloroformate (6.49 mL, 49.4 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 (90 mL, 135 mmol) in toluene (1.5 M) was added. The mixture was stirred at the same temperature for 1.5 h, LCMS indicated completion of the reaction. The reaction was quenched with sat. NH4Cl (aq.), and subsequently warmed up to r.t. concentrated, diluted with sat. NH4Cl and extracted with dichloromethane twice. The organic phase was filtered through Celite to remove gummy precipitate, and was then washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo to afford 1-ethyl-3-(hydroxymethyl)-7,8-bis((4-methoxybenzyl)oxy)quinolin-4(1H)-one (20 g, 23.55 mmol, 52.4% yield) as yellow solid, which was used in the next oxidation step without further purification. LCMS: (M+H)+: 476.3.

Workup

  1. temperatureThen the mixture was cooled down to −78° C.
  2. stirringThe mixture was stirred at the same temperature for 1.5 h
  3. customcompletion of the reaction
  4. customThe reaction was quenched with sat. NH4Cl (aq.)
  5. temperaturesubsequently warmed up to r.t.
  6. concentrationconcentrated
  7. additiondiluted with sat. NH4Cl
  8. extractionextracted with dichloromethane twice
  9. filtrationThe organic phase was filtered through Celite
  10. customto remove gummy precipitate
  11. washwas then washed with brine
  12. dry with materialdried over sodium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-29a0efe8ed2546ad8602de7c4fbce1f9
Source dataset
uspto-grants-2016_05
Patent number
US09340556B2

Reaction notes

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