5-Benzyloxy-2-fluoro-4-methylphenol → 4-(5-Benzyloxy-2-fluoro-4-methylphenoxy)-6-methoxy-7-(3-morpholinopropoxy)quinoline

HRID 393600

Reaction equation

Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH2:15][CH2:16][CH2:17][N:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][CH:3]=1.[CH2:24]([O:31][C:32]1[C:33]([CH3:40])=[CH:34][C:35]([F:39])=[C:36]([OH:38])[CH:37]=1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.CC(C)([O-])C.[K+]>CS(C)=O>[CH2:24]([O:31][C:32]1[C:33]([CH3:40])=[CH:34][C:35]([F:39])=[C:36]([CH:37]=1)[O:38][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH2:15][CH2:16][CH2:17][N:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][CH:3]=1)[C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1

Participants

Conditions

Temperature: 160 °C

Procedure

4-Chloro-6-methoxy-7-(3-morpholinopropoxy)quinoline (250 mg, 0.74 mmol) was added to a solution of 5-benzyloxy-2-fluoro-4-methylphenol (257 mg 1.1 mmol) and potassium t-butoxide (125 mg, 1.1 mmol) in DMSO (3 ml) and the mixture heated at 160° C. for 1.5 hours. The mixture was allowed to cool and was partitioned between water and ethyl acetate. The organic layer was separated, washed with brine, dried (MgSO4), and the solvent removed by evaporation. The residue was purified by column chromatography eluting with methylene chloride/methanol (95/5) to give 4-(5-benzyloxy-2-fluoro-4-methylphenoxy)-6-methoxy-7-(3-morpholinopropoxy)quinoline (105 mg, 69%).

Workup

temperatureto cool
customwas partitioned between water and ethyl acetate
customThe organic layer was separated
washwashed with brine
dry with materialdried (MgSO4)
customthe solvent removed by evaporation
customThe residue was purified by column chromatography
washeluting with methylene chloride/methanol (95/5)

Sources & evidence

ORD record: ord-5a38eee06c30427a9e107d76bcd0c311
Source dataset: uspto-grants-2004_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06809097B1

Linked notes

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