Potassium Carbonate → 3-bromo-4-[(2,4-difluorobenzyl)oxy]quinolin-2(1H)-one

HRID 1867176Notes

Reaction equation

HRID 1867176 reaction equation
[OH:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[NH:5][C:4](=[O:12])[CH:3]=1.[Br:13]C1CC(=O)NC1=O.C([O-])([O-])=O.[K+].[K+].[F:27][C:28]1[CH:35]=[C:34]([F:36])[CH:33]=[CH:32][C:29]=1[CH2:30]Br>C(Cl)Cl.CN(C=O)C>[Br:13][C:3]1[C:4](=[O:12])[NH:5][C:6]2[C:11]([C:2]=1[O:1][CH2:30][C:29]1[CH:32]=[CH:33][C:34]([F:36])=[CH:35][C:28]=1[F:27])=[CH:10][CH:9]=[CH:8][CH:7]=2

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 38309BromosuccinimideHCID 902971-(Bromomethyl)-2,4-difluorobenzeneHCID 546808712(1H)-Quinolinone, 4-hydroxy-

Product 1

HCID 220499763-bromo-4-[(2,4-difluorobenzyl)oxy]quinolin-2(1H)-one

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a room temperature solution of 4-hydroxy-1,2-dihydroquinolin-2-one (500 mg, 3.10 mmol) in CH2Cl2 (10.0 mL) was added portion-wise solid N bromosuccinimide (551.5 mg, 3.10 mmol). The reaction was stirred vigorously for 1.0 h, followed by the sequential addition of K2CO3 (540 mg, 3.90 mmol), DMF (4.0 mL), and 2,4-difluorobenzyl bromide (0.430 mL, 3.30 mmol). The resulting suspension was stirred for 4.5 hours until complete formation of desired product was seen by LCMS analysis. The reaction was then diluted with ethyl acetate (400 mL) and brine washed (3×200 mL). The resulting organic extract was Na2SO4 dried, filtered, and concentrated in vacuo to a residue that was subjected to SiO2 chromatography with ethyl acetate/hexanes/methanol (60:35:5) to furnish a solid (529 mg, 47%). 1H NMR (300 MHz, d6-DMSO) δ 12.23 (s, 1H), 7.68 (app q, J=7.5 Hz, 1H), 7.64 (app q, J=8.5 Hz, 1H), 7.54 (app q, J=8.3 Hz, 1H), 7.38-7.27 (m, 2H), 7.20 (app t, J=7.4 Hz, 1H), 7.13 (app dt, J=8.4, 2.6 Hz, 1H), 5.25 (s, 2H); LC/MS C-18 column, tr=2.64 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50° C.). ES-MS m/z 366 (M+H). ES-HRMS m/z 365.9967 (M+H calcd for C16H11BrF2NO2 requires 365.9936).

Sources & evidence

ORD record
ord-e10c1cd3cc554e3b8158626c29319a3b
Source dataset
uspto-grants-2009_12
Patent number
US07629363B2

Reaction notes

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