Triethylamine → HCID 86732765, compound

HRID 525902Notes

Reaction equation

HRID 525902 reaction equation
[Cl:1][C:2]1[C:11]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=2)=[C:10]([O:22][CH2:23][C:24]2[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=2)[CH:9]=[C:8]2[C:3]=1[C:4](=[O:37])[C:5]([C:34](O)=[O:35])=[CH:6][N:7]2[CH2:32][CH3:33].C(N(CC)CC)C.ClC(OCC(C)C)=O.CC(C[AlH]CC(C)C)C>O1CCCC1.C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=2)=[C:10]([O:22][CH2:23][C:24]2[CH:25]=[CH:26][C:27]([O:30][CH3:31])=[CH:28][CH:29]=2)[CH:9]=[C:8]2[C:3]=1[C:4](=[O:37])[C:5]([CH2:34][OH:35])=[CH:6][N:7]2[CH2:32][CH3:33]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 14487Diisobutylaluminum hydrideHCID 62365Isobutyl chloroformateHCID 86732764HCID 86732764, compound

Product 1

HCID 86732765HCID 86732765, compoundYield 74.2%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of 5-chloro-1-ethyl-6,7-bis((4-methoxybenzyl)oxy)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (24 g, 41.7 mmol) in Tetrahydrofuran (THF) (450 mL) was added triethylamine (8.71 mL, 62.5 mmol), followed by careful addition of isobutyl chloroformate (7.66 mL, 58.4 mmol). The resulting mixture was stirred at r.t. for 2.5 h. Then the mixture was cooled down to −40° C. and a solution of DIBAL-H (69.5 mL, 104 mmol) in toluene (1.5 M) was added. The mixture was stirred at the same temperature for 3.5 h. After completion, the reaction was quenched with sat. NH4Cl (aq.), warmed up to r.t., diluted with sat. NH4Cl (aq.), filtered through Celite to remove gummy precipitate, and extracted with dichloromethane twice. The combined organic extracts were then saturated with brine and then dried over sodium sulfate, filtered and the resulting filtrate was concentrated in vacuo to afford 5-chloro-1-ethyl-3-(hydroxymethyl)-6,7-bis((4-methoxybenzyl)oxy)quinolin-4(1H)-one (19 g, 30.9 mmol, 74.2% yield) as a yellow solid, which was used in the next oxidation step. LCMS: (M+H)+: 510.0.

Workup

  1. temperatureThen the mixture was cooled down to −40° C.
  2. stirringThe mixture was stirred at the same temperature for 3.5 h
  3. customAfter completion, the reaction was quenched with sat. NH4Cl (aq.)
  4. temperaturewarmed up to r.t.
  5. additiondiluted with sat. NH4Cl (aq.)
  6. filtrationfiltered through Celite
  7. customto remove gummy precipitate
  8. extractionextracted with dichloromethane twice
  9. dry with materialsaturated with brine and then dried over sodium sulfate
  10. filtrationfiltered
  11. concentrationthe resulting filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-f7982bf68cac4c1e9901cdc12e314086
Source dataset
uspto-grants-2016_05
Patent number
US09340556B2

Reaction notes

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