Pyridine → Ethyl 3-{[(benzyloxy)carbonyl]amino}-7-bromo-6-fluoroquinoline-2-carboxylate

HRID 924380Notes

Reaction equation

[NH2:1][C:2]1[C:3]([C:14]([O:16][CH2:17][CH3:18])=[O:15])=[N:4][C:5]2[C:10]([CH:11]=1)=[CH:9][C:8]([F:12])=[C:7]([Br:13])[CH:6]=2.N1C=CC=CC=1.Cl[C:26]([O:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)=[O:27]>C(Cl)Cl.CCOC(C)=O>[CH2:29]([O:28][C:26]([NH:1][C:2]1[C:3]([C:14]([O:16][CH2:17][CH3:18])=[O:15])=[N:4][C:5]2[C:10]([CH:11]=1)=[CH:9][C:8]([F:12])=[C:7]([Br:13])[CH:6]=2)=[O:27])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1

Participants

Conditions

Temperature: -10 °C

Procedure

DCM (10.0 mL) was added to a mixture of ethyl 3-amino-7-bromo-6-fluoroquinoline-2-carboxylate (882.5 mg, 2.818 mmol) and pyridine (592.1 mg, 7.485 mmol). The mixture was cooled to −10° C. A solution of benzyl chloroformate (650.6 mg, 3.623 mmol) in DCM (5.0 mL) was added slowly over a period of 5 min. The mixture was then allowed to warm to room temperature and was stirred for 2 h. The reaction mixture was diluted with EtOAc (100 mL), washed with saturated aq. NaHCO3 (100 mL) and brine (100 mL), then dried over Na2SO4 and concentrated under reduced pressure. The resulting residue was purified by flash chromatography on silica gel (0-30% EtOAc in hexanes) to give the sub-title compound as an off-white solid (854.9, 68%). LCMS calc. for C20H17BrFN2O4 (M+H)+: m/z=447.0. found 447.0.

Workup

temperatureto warm to room temperature
washwashed with saturated aq. NaHCO3 (100 mL) and brine (100 mL)
dry with materialdried over Na2SO4
concentrationconcentrated under reduced pressure
customThe resulting residue was purified by flash chromatography on silica gel (0-30% EtOAc in hexanes)

Sources & evidence

ORD record: ord-aff41ac08d8a4fd8becb9481a10986d5
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09278950B2

Reaction notes

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