Diisobutylaluminum hydride → HCID 86732758, compound

HRID 525892Notes

Reaction equation

HRID 525892 reaction equation
[CH2:1]([N:3]1[C:12]2[C:7](=[CH:8][C:9]([O:24][CH2:25][C:26]3[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=3)=[C:10]([O:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=3)[C:11]=2[F:13])[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](=[CH:8][C:9]([O:24][CH2:25][C:26]3[CH:27]=[CH:28][C:29]([O:32][CH3:33])=[CH:30][CH:31]=3)=[C:10]([O:14][CH2:15][C:16]3[CH:17]=[CH:18][C:19]([O:22][CH3:23])=[CH:20][CH:21]=3)[C:11]=2[F:13])[C:6](=[O:34])[C:5]([CH2:35][OH:36])=[CH:4]1)[CH3:2]

Participants

6

Reactant 3

HCID 14487Diisobutylaluminum hydrideHCID 62365Isobutyl chloroformateHCID 86732756HCID 86732756, compound

Product 1

HCID 86732758HCID 86732758, compoundYield 68.6%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of 1-ethyl-8-fluoro-6,7-bis((4-methoxybenzyl)oxy)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (15 g, 29.6 mmol) in Tetrahydrofuran (THF) (100 mL) was added TEA (6.18 mL, 44.3 mmol) and isobutyl chloroformate (5.82 mL, 44.3 mmol). The resulting mixture was stirred at r.t. for 1 h. The mixture was then cooled down to −40° C. and a solution of DIBAL-H (49.3 mL, 73.9 mmol) in toluene (1.5 M) was added. The mixture was stirred at the same temperature for 1.5 h, when LCMS indicated completion of the reaction. The reaction was quenched with sat. NH4Cl (aq.), warmed up to r.t. and concentrated. The mixture was diluted with sat. NH4Cl and extracted with dichloromethane (2×30 mL). The combined organic solution was then dried over sodium sulfate, filtered and concentrated in vacuo to afford 1-ethyl-8-fluoro-3-(hydroxymethyl)-6,7-bis((4-methoxybenzyl)oxy)quinolin-4(1H)-one (10 g, 20.26 mmol, 68.6% yield) as a yellow solid, which was used in the next oxidation step without further purification.

Workup

  1. temperatureThe mixture was then cooled down to −40° 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. temperaturewarmed up to r.t.
  6. concentrationconcentrated
  7. additionThe mixture was diluted with sat. NH4Cl
  8. extractionextracted with dichloromethane (2×30 mL)
  9. dry with materialThe combined organic solution was then dried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-bc721642330944b1bca34a95f9059520
Source dataset
uspto-grants-2016_05
Patent number
US09340556B2

Reaction notes

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