Isopropanol → (5-(2-(dimethylamino)ethoxy)pyridin-2-yl)(4-(tetrahydro-2H-pyran-2-yloxy)phenyl)methanone

HRID 626152Notes

Reaction equation

I[C:2]1[CH:14]=[CH:13][C:5]([O:6][CH:7]2[CH2:12][CH2:11][CH2:10][CH2:9][O:8]2)=[CH:4][CH:3]=1.CCCCCC.[CH3:21][N:22]([CH3:38])[CH2:23][CH2:24][O:25][C:26]1[CH:27]=[CH:28][C:29]([C:32](N(OC)C)=[O:33])=[N:30][CH:31]=1.C(O)(C)C>C1COCC1.O>[CH3:21][N:22]([CH3:38])[CH2:23][CH2:24][O:25][C:26]1[CH:27]=[CH:28][C:29]([C:32]([C:2]2[CH:14]=[CH:13][C:5]([O:6][CH:7]3[CH2:12][CH2:11][CH2:10][CH2:9][O:8]3)=[CH:4][CH:3]=2)=[O:33])=[N:30][CH:31]=1

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of 2-(4-iodophenoxy)tetrahydro-2H-pyran (1.1 eq) in THF was added a solution of nbutyllitium in hexane (1.1 eq) at −78° C. The mixture was stirred at −78° C. for 20 min. To the mixture was added a solution of 5-(2-(dimethylamino)-ethoxy)-N-methoxy-N-methylpicolinamide (1.0 eq) in THF at −78° C. After 2 h, isopropanol and water was added to the mixture, and the cold bath was removed. The mixture was stirred at room temperature for 20 min. The mixture was extracted with ethyl acetate. The extract was washed with 0.5 N HCl, sodium bicarbonate (sat.), and brine, dried over sodium sulfate, filtered, concentrated, and purified by column chromatography (silica gel) to give the subtitle compound (47% yield).

Workup

waitAfter 2 h
customthe cold bath was removed
stirringThe mixture was stirred at room temperature for 20 min
extractionThe mixture was extracted with ethyl acetate
washThe extract was washed with 0.5 N HCl, sodium bicarbonate (sat.), and brine
dry with materialdried over sodium sulfate
filtrationfiltered
concentrationconcentrated
custompurified by column chromatography (silica gel)

Sources & evidence

ORD record: ord-51921f24e10b479c950a043a97582218
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09309211B2

Reaction notes

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