Morpholine → 4-(5-Bromopyridin-3-yl)morpholine

HRID 573600

Reaction equation

HRID 573600 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Br:8])[CH:7]=1.CC(C)([O-])C.[Na+].[NH:15]1[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>[Br:8][C:6]1[CH:7]=[C:2]([N:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)[CH:3]=[N:4][CH:5]=1

Participants

7

Reactant 3

HCID 8083MorpholineHCID 693693,5-DibromopyridineHCID 23676156Sodium t-butoxide

Product 1

HCID 467396144-(5-Bromopyridin-3-yl)morpholineYield 89.3%

Reagents, catalysts & solvents 3

HCID 634876Binap, (A+-)-CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 3,5-dibromopyridine (2.121 g, 8.95 mmol), BINAP (0.279 g, 0.448 mmol), Pd2(dba)3 (0.137 g, 0.149 mmol) and sodium tert-butoxide (1.434 g, 14.92 mmol) in toluene (50 mL) was added morpholine (0.65 mL, 7.46 mmol). The mixture was then heated at 120° C. for ca. 5 h. After cooling to RT, the reaction mixture was filtered through celite and the filtrate was concentrated. The residue was purified by normal phase chromatography, eluting with a gradient of 0-50% ethyl acetate in DCM, to give the title compound (1.62 g). LCMS (A) m/z: 243/245 [M+1]+, Rt 0.83 min (acidic),

Workup

  1. temperatureAfter cooling to RT
  2. filtrationthe reaction mixture was filtered through celite
  3. concentrationthe filtrate was concentrated
  4. customThe residue was purified by normal phase chromatography
  5. washeluting with a gradient of 0-50% ethyl acetate in DCM

Sources & evidence

ORD record
ord-b1da736e096c4c6d9ff687d87264a164
Source dataset
uspto-grants-2015_05
Patent number
US09029545B2

Linked notes

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