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

HRID 1832123Notes

Reaction equation

HRID 1832123 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]N1C(=O)CCC1=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 67184N-bromobutanimideHCID 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). Step 2: Preparation of methyl 4-{[3-bromo-4-[(2,4-difluorobenzyl)oxy]-2-oxoquinolin-1(2H)-yl]methyl}benzoate.

Sources & evidence

ORD record
ord-c470b3a6844c4190a6a5e2b60ec3a90d
Source dataset
uspto-grants-2006_06
Patent number
US07067540B2

Reaction notes

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