Thionyl Chloride → ethyl6-bromo-4-chloro-7-fluoroquinoline-3-carboxylate

HRID 1486934Notes

Reaction equation

S(Cl)([Cl:3])=O.[Br:5][C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][C:15]=1[F:16])[NH:12][CH:11]=[C:10]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[C:9]2=O>CN(C=O)C>[Br:5][C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][C:15]=1[F:16])[N:12]=[CH:11][C:10]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[C:9]2[Cl:3]

Participants

Conditions

Temperature: 80 °C

Procedure

Thionyl chloride (150 mL, 2.08 mol) was added to a solution of ethyl 6-bromo-7-fluoro-4-oxo-1H-quinoline-3-carboxylate (25 g, 79.59 mmol) in DMF (50 mL) and the solution stirred at 80° C. for 4 h. The mixture was concentrated under vacuum and quenched by the addition of ice/water. The reaction mixture was extracted with DCM (8×100 mL), the organic extracts combined and the mixture adjusted to pH=7 by the addition of 1.5M ammonium hydrogen carbonate. The resulting mixture was washed with water (3×100 mL), the organics dried over Na2SO4 and concentrated in vacuo to afford the desired material (20 g, 76%) as a light yellow solid which was used without further purification. NMR Spectrum: 1H NMR (400 MHz, CDCl3) δ 1.49-1.42 (3H, m), 4.54-4.82 (2H, q), 7.86 (1H, d), 8.69 (1H, d), 9.23 (1H, s). Mass Spectrum: m/z (ES+)[M+H]+=334.

Workup

concentrationThe mixture was concentrated under vacuum
customquenched by the addition of ice/water
extractionThe reaction mixture was extracted with DCM (8×100 mL)
additionthe mixture adjusted to pH=7 by the addition of 1.5M ammonium hydrogen carbonate
washThe resulting mixture was washed with water (3×100 mL)
dry with materialthe organics dried over Na2SO4
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-cc7650c7799d4af2b446a0080935bc2f
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09428503B2

Reaction notes

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