Dimethylformamide → Ethyl 2-(2-chloro-7-((3-chlorobenzyl)oxy)quinolin-3-yl)acetate

HRID 513951Notes

Reaction equation

HRID 513951 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:24]=[CH:25][CH:26]=1)[CH2:5][O:6][C:7]1[CH:16]=[C:15]2[C:10]([CH:11]=[C:12]([CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20])[C:13](=O)[NH:14]2)=[CH:9][CH:8]=1.C(Cl)(=O)C([Cl:30])=O.CN(C=O)C>C(Cl)(Cl)Cl>[Cl:30][C:13]1[C:12]([CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20])=[CH:11][C:10]2[C:15](=[CH:16][C:7]([O:6][CH2:5][C:4]3[CH:24]=[CH:25][CH:26]=[C:2]([Cl:1])[CH:3]=3)=[CH:8][CH:9]=2)[N:14]=1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 90417406HCID 90417406, compound

Product 1

HCID 90417116Ethyl 2-(2-chloro-7-((3-chlorobenzyl)oxy)quinolin-3-yl)acetateYield 89%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a slurry of ethyl 2-(7-((3-chlorobenzyl)oxy)-2-oxo-1,2-dihydroquinolin-3-yl)acetate (31.4 g, 0.08 mol) in chloroform (314 mL) at ambient temperature was added oxalyl dichloride (21.7 mL, 0.25 mol) and DMF (0.66 mL, 0.01 mol). The resulting slurry was heated to reflux for 1 h. The reaction was quenched with sat. aqueous NaHCO3 (400 mL). The aqueous layer was extracted with DCM (2×200 mL) and the combined organic layers were washed with brine and dried over Na2SO4. The organic layer was concentrated under reduced pressure to furnish a black solid that was triturated in 1:1 EtOAc:hexanes (400 mL) and filtered. The solid was recrystallized from MeOH to furnish (17.0 g, 52%). Two additional crops of product were acquired from the mother liquor to furnish a total of 27.8 g (84.3%) of the title compound. 1H NMR (400 MHz, DMSO-d6) δ 8.34 (s, 1H), 7.93 (d, J=9.0 Hz, 1H), 7.59 (s, 1H), 7.51-7.37 (m, 5H), 5.31 (s, 2H), 4.13 (q, J=7.1 Hz, 2H), 3.94 (s, 2H), 1.19 (t, J=7.1 Hz, 3H). [M+H]=390.2

Workup

  1. temperatureThe resulting slurry was heated
  2. temperatureto reflux for 1 h
  3. customThe reaction was quenched with sat. aqueous NaHCO3 (400 mL)
  4. extractionThe aqueous layer was extracted with DCM (2×200 mL)
  5. washthe combined organic layers were washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationThe organic layer was concentrated under reduced pressure
  8. customto furnish a black solid
  9. customthat was triturated in 1:1 EtOAc
  10. filtrationhexanes (400 mL) and filtered
  11. customThe solid was recrystallized from MeOH
  12. customto furnish (17.0 g, 52%)

Sources & evidence

ORD record
ord-cf2153dd18fc4b01b74d3a4d942a995b
Source dataset
uspto-grants-2015_08
Patent number
US09102674B2

Reaction notes

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