6-Hydroxy-3,4-dihydro-2(1H)-quinolinone → 6-(1-cyclobutylpiperidin-4-yloxy)-3,4-dihydroquinolin-2(1H)-one

HRID 1913882Notes

Reaction equation

HRID 1913882 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=[O:12])[CH2:6][CH2:5]2.[CH:13]1([N:17]2[CH2:22][CH2:21][CH:20](O)[CH2:19][CH2:18]2)[CH2:16][CH2:15][CH2:14]1>O1CCCC1.N(C(OCC)=O)=NC(OCC)=O>[CH:13]1([N:17]2[CH2:22][CH2:21][CH:20]([O:1][C:2]3[CH:3]=[C:4]4[C:9](=[CH:10][CH:11]=3)[NH:8][C:7](=[O:12])[CH2:6][CH2:5]4)[CH2:19][CH2:18]2)[CH2:16][CH2:15][CH2:14]1

Participants

5

Reactant 2

HCID 27740406-Hydroxy-3,4-dihydro-2(1H)-quinolinoneHCID 581554161-Cyclobutylpiperidin-4-ol

Product 1

HCID 666826006-(1-cyclobutylpiperidin-4-yloxy)-3,4-dihydroquinolin-2(1H)-oneYield 25%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 220568ethyl N-ethoxycarbonyliminocarbamateSolvent

Procedure

Under a nitrogen atmosphere, to a solution of 6-hydroxy-3,4-dihydroquinolin-2(1H)-one (5.00 g) and N-cyclobutyl-4-hydroxypiperidine (which can be synthesized as described in WO2005/108384) (7.10 g) in tetrahydrofuran (50 mL), diethyl azodicarboxylate (40% in toluene, 16.7 mL) was added dropwise under ice cooling. After completion of the dropwise addition, the reaction mixture was warmed to room temperature and stirred for 40 hours. The reaction mixture was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (eluting solvent: chloroform/methanol=95/5) to give the titled compound (2.30 g, 25%) as a colorless powder.

Workup

  1. additionAfter completion of the dropwise addition
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. customthe resulting residue was purified by silica gel column chromatography (eluting solvent: chloroform/methanol=95/5)

Sources & evidence

ORD record
ord-e8ce6f106281409c8258bc646014bb99
Source dataset
uspto-grants-2013_12
Patent number
US08609847B2

Reaction notes

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