Benzyl Bromide → 5-benzyloxy-6-bromo-4-(trifluoromethyl)-1H-quinolin-2-one

HRID 1350135Notes

Reaction equation

[Br:1][C:2]1[C:3]([OH:17])=[C:4]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=[O:12])[CH:6]=[C:5]2[C:13]([F:16])([F:15])[F:14].[F-].[Cs+].[CH2:20](Br)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.OS([O-])(=O)=O.[Na+]>CN(C=O)C>[CH2:20]([O:17][C:3]1[C:2]([Br:1])=[CH:11][CH:10]=[C:9]2[C:4]=1[C:5]([C:13]([F:16])([F:15])[F:14])=[CH:6][C:7](=[O:12])[NH:8]2)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a suspension of 6-bromo-5-hydroxy-4-(trifluoromethyl)-1H-quinolin-2-one (9.42 g, 30.6 mmol) and CsF (13.9 g, 91.7 mmol) in 102 mL DMF was added benzyl bromide (6.54 g, 38.2 mmol) dropwise. After 24 h, the mixture was poured into 0.1 M NaHSO4 (500 mL) and extracted with EtOAc (1:1). The aqueous layer was reextracted with EtOAc (500 mL) and the combined organic layers were washed sequentially with water (500 mL), brine (300 mL), dried over MgSO4, filtered and concentrated to a slurry. The mixture was cooled to 0° C., filtered and the resultant solids washed with cold EtOAc to afford 7.26 g (60%) of 5-benzyloxy-6-bromo-4-(trifluoromethyl)-1H-quinolin-2-one, a tan solid. Rf 0.26 (7:3 hexanes:acetone); 1H NMR (400 MHz, acetone-d6) δ 11.3 (broad s, 1H), 7.91 (d, 1H, J=9.0, 1H), 7.61 (d, 2H, J=7.3), 7.43 (t, 2H, J=7.2), 7.25–7.35 (m, 1H), 7.32 (d, 1H, J=9.0), 7.06 (s, 1H), 5.10 (s, 1H).

Workup

extractionextracted with EtOAc (1:1)
washthe combined organic layers were washed sequentially with water (500 mL), brine (300 mL)
dry with materialdried over MgSO4
filtrationfiltered
concentrationconcentrated to a slurry
filtrationfiltered
washthe resultant solids washed with cold EtOAc

Sources & evidence

ORD record: ord-4895ada18c0140db9a63de430785e2e0
Source dataset: uspto-grants-2007_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07214690B2

Reaction notes

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