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

HRID 1832123Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1832123
[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

Komponenten

7

Edukt 4

HCID 11430Potassium CarbonateHCID 67184N-bromobutanimideHCID 902971-(Bromomethyl)-2,4-difluorobenzeneHCID 546808712,4-Dihydroxyquinoline

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

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.

Quellen und Nachweise

ORD-Eintrag
ord-c470b3a6844c4190a6a5e2b60ec3a90d
Quelldatensatz
uspto-grants-2006_06
Patentnummer
US07067540B2

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