Potassium Carbonate → cis-4-(6-Bromo-2-pyridinyl)-2,6-dimethylmorpholine

HRID 2278424Notes

Reaction equation

[CH3:1][C@H:2]1[O:7][C@@H:6]([CH3:8])[CH2:5][NH:4][CH2:3]1.[Br:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12](Br)[N:11]=1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[Br:9][C:10]1[N:11]=[C:12]([N:4]2[CH2:5][C@H:6]([CH3:8])[O:7][C@H:2]([CH3:1])[CH2:3]2)[CH:13]=[CH:14][CH:15]=1

Participants

Conditions

Temperature: 120 °C

Procedure

cis-2,6-Dimethylmorpholine (0.535 g, 4.64 mmol) was added to a suspension of 2,6-dibromopyridine (1 g, 4.22 mmol) and potassium carbonate (1.750 g, 12.66 mmol) in anhydrous acetonitrile (35 mL). After addition, the reaction mixture was stirred at 120° C. overnight. Crude LC/MS showed starting material and desired product so cis-2,6-dimethylmorpholine (185 mg, 1.61 mmol) was added to the reaction mixture which was then stirred at 120° C. overnight. Crude LC/MS showed desired product can be seen and no starting material left, so the reaction mixture was diluted with ethyl acetate (100 mL) and water (50 mL). The organic layer was separated and the aqueous layer was extracted with ethyl acetate (2×100 mL). The combined organic layers were dried (sodium sulfate), filtered and concentrated under reduced pressure. The residue was dissolved in dichloromethane (˜10 ml) and purified on silica by a Biotage SP4 chromatographic system (40+M cartridge, eluted with 0-100% ethyl acetate in isohexanes). Fractions containing pure product were combined and concentrated under reduced pressure to give the title compound as a colourless oil (705 mg, 2.340 mmol, 55.4% yield). LC/MS [M+H]+=271/273.

Workup

additionAfter addition

Sources & evidence

ORD record: ord-2b999aa314e64ce48cf06e1e0afcadd0
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09133178B2

Reaction notes

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