1-Chloro-4-(chloromethyl)benzene → Ethyl 7-[(4-chlorophenyl)methoxy]quinoline-3-carboxylate

HRID 1748378Notes

Reaction equation

HRID 1748378 reaction equation
[OH:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH:8]=[N:9]2)=[CH:4][CH:3]=1.C([O-])([O-])=O.[Cs+].[Cs+].[Cl:23][C:24]1[CH:31]=[CH:30][C:27]([CH2:28]Cl)=[CH:26][CH:25]=1>CN(C=O)C>[Cl:23][C:24]1[CH:31]=[CH:30][C:27]([CH2:28][O:1][C:2]2[CH:11]=[C:10]3[C:5]([CH:6]=[C:7]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH:8]=[N:9]3)=[CH:4][CH:3]=2)=[CH:26][CH:25]=1

Participants

5

Reactant 3

HCID 77231-Chloro-4-(chloromethyl)benzeneHCID 10796Cesium carbonateHCID 135819170HCID 135819170, compound2×

Product 1

HCID 81689721Ethyl 7-[(4-chlorophenyl)methoxy]quinoline-3-carboxylateYield 63.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of ethyl 7-hydroxyquinoline-3-carboxylate (Intermediate 1, 50 mg, 0.23 mmol) in DMF (1.15 mL) was added Cs2CO3 (150 mg, 0.46 mmol) and 4-chlorobenzyl chloride (41 mg, 0.25 mmol). The reaction was stirred overnight at ambient temperature. The reaction mixture was loaded directly onto a column and purification (FCC, SiO2, EtOAc/hexanes, 0-20%) afforded the title compound as a white solid (50 mg, 63%). 1H NMR (400 MHz, CDCl3) δ 9.37 (d, J=2.3 Hz, 1H), 8.74 (d, J=2.0 Hz, 1H), 7.83 (d, J=9.0 Hz, 1H), 7.50 (d, J=2.3 Hz, 1H), 7.45-7.35 (m, 4H), 7.34-7.29 (m, 1H), 5.20 (s, 2H), 4.45 (q, J=7.3 Hz, 2H), 1.44 (t, J=7.0 Hz, 3H). [M+H]=342.3.

Workup

  1. customThe reaction mixture was loaded directly onto a column and purification (FCC, SiO2, EtOAc/hexanes, 0-20%)

Sources & evidence

ORD record
ord-9f896f2149104648a27748efa009318f
Source dataset
uspto-grants-2015_10
Patent number
US09150572B2

Reaction notes

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