Morpholine → 3-Methanesulfonyl-2-methyl-6-morpholin-4-yl-4-(4-trifluoromethyl-phenyl)-quinoline

HRID 13671Notes

Reaction equation

C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[C:42]1[CH:43]=[C:44]2[C:49](=[CH:50][CH:51]=1)[N:48]=[C:47]([CH3:52])[C:46]([S:53]([CH3:56])(=[O:55])=[O:54])=[C:45]2[C:57]1[CH:62]=[CH:61][C:60]([C:63]([F:66])([F:65])[F:64])=[CH:59][CH:58]=1.[NH:67]1[CH2:72][CH2:71][O:70][CH2:69][CH2:68]1>C(O)(C)(C)C.CCCCCCC>[CH3:56][S:53]([C:46]1[C:47]([CH3:52])=[N:48][C:49]2[C:44]([C:45]=1[C:57]1[CH:58]=[CH:59][C:60]([C:63]([F:64])([F:66])[F:65])=[CH:61][CH:62]=1)=[CH:43][C:42]([N:67]1[CH2:72][CH2:71][O:70][CH2:69][CH2:68]1)=[CH:51][CH:50]=2)(=[O:54])=[O:55]

Participants

Conditions

Temperature: 110 °C

Procedure

A tube placed under argon was charged with tris(dibenzylideneacetone)dipalladium chloroform complex (51 mg, 0.05 mmol), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (47 mg, 0.10 mmol) and cesium carbonate (1.21 g, 3.71 mmol). 6-Bromo-3-methanesulfonyl-2-methyl-4-(4-trifluoromethyl-phenyl)-quinoline (compound of example 20) (800 mg, 1.95 mmol) in tert.-butanol (20 ml) was added, followed by morpholine (0.259 g, 2.97 mmol). The tube was sealed and heated at 110° C. for 2 h. The reaction mixture was cooled to 20° C., diluted with heptane, filtered through dicalite and purified directly by flash chromatography on silica gel in heptane/ethyl acetate with a gradient 100:0 to 40:60 to give a yellow solid (320 mg, 29%). MS: m/z=451 (M+H).

Workup

customA tube placed under argon
customThe tube was sealed
temperatureThe reaction mixture was cooled to 20° C.
filtrationfiltered through dicalite
custompurified directly by flash chromatography on silica gel in heptane/ethyl acetate with a gradient 100:0 to 40:60

Sources & evidence

ORD record: ord-c68031c6420a4cc39c7e9bc62056b4b6
Source dataset: uspto-grants-2010_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07728142B2

Reaction notes

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