Cesium carbonate → (R)-6-fluoro-7-(2-methoxypropoxy)-2-methylquinoline

HRID 339089Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[OH:12])[N:8]=[C:7]([CH3:13])[CH:6]=[CH:5]2.C([O-])([O-])=O.[Cs+].[Cs+].CC1C=CC(S(O[CH2:31][C@H:32]([O:34][CH3:35])[CH3:33])(=O)=O)=CC=1>CN1C(=O)CCC1>[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[O:12][CH2:31][C@H:32]([O:34][CH3:35])[CH3:33])[N:8]=[C:7]([CH3:13])[CH:6]=[CH:5]2

Participants

Conditions

Temperature: 80 °C

Procedure

To a stirred mixture of 6-fluoro-2-methylquinolin-7-ol (0.200 g, 1.13 mmol), Cs2CO3 (0.552 g, 1.69 mmol) and NMP (2.3 mL) was added (R)-2-methoxypropyl 4-methylbenzenesulfonate (0.303 g, 1.24 mmol). The reaction mixture was heated at 80° C. for 1 hour. After cooling, the reaction was partitioned between toluene and water. The aqueous layer was extracted with toluene (2×). The combined organic layers were washed with water and brine, dried and concentrated. The residue was purified by flash chromatography on silica gel (hexanes:EtOAc, 1:1) to give (R)-6-fluoro-7-(2-methoxypropoxy)-2-methylquinoline (0.289 g, 103%).

Workup

temperatureAfter cooling
customthe reaction was partitioned between toluene and water
extractionThe aqueous layer was extracted with toluene (2×)
washThe combined organic layers were washed with water and brine
customdried
concentrationconcentrated
customThe residue was purified by flash chromatography on silica gel (hexanes:EtOAc, 1:1)

Sources & evidence

ORD record: ord-d997d4e43a6349709a37cb58506571f9
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08889704B2

Reaction notes

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