Morpholine → HCID 59526391, compound

HRID 385731Notes

Reaction equation

HRID 385731 reaction equation
Br[C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[C:4]([F:9])[CH:3]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C(=O)([O-])[O-].[K+].[K+].[NH:50]1[CH2:55][CH2:54][O:53][CH2:52][CH2:51]1>C(OCC)C.O.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]>[F:9][C:4]1[CH:3]=[C:2]([N:50]2[CH2:55][CH2:54][O:53][CH2:52][CH2:51]2)[CH:7]=[C:6]([F:8])[CH:5]=1

Participants

8

Reactant 4

HCID 8083MorpholineHCID 11430Potassium CarbonateHCID 1363131-Bromo-3,5-difluorobenzeneHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl

Product 1

HCID 59526391HCID 59526391, compound

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 3283Diethyl EtherSolvent

Procedure

A sealed tube was charged with 1-bromo-3,5-difluorobenzene (1.79 ml, 15.5 mmol), Pd2(dba)3 (0.85 g, 0.93 mmol), X-PHOS (2.22 g, 4.66 mmol), and potassium carbonate (4.73 g, 34.2 mmol). The tube was evacuated and backfilled with argon 3×. Fully degassed tert-amyl alcohol (51 mL) was added followed immediately by the addition of morpholine (2.71 ml, 31.1 mmol). The tube was then sealed and placed in an oil bath at 100° C. and stirred overnight. The reaction mixture was taken up in diethyl ether and water. The aqueous layer was extracted twice with diethyl ether. The organics were combined, dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. Purification via flash chromatography (silica, 0-17% diethylether/hexanes) afforded the title compound as a light yellow solid.

Workup

  1. customThe tube was evacuated
  2. additionFully degassed tert-amyl alcohol (51 mL) was added
  3. customThe tube was then sealed
  4. customplaced in an oil bath at 100° C.
  5. extractionThe aqueous layer was extracted twice with diethyl ether
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customPurification via flash chromatography (silica, 0-17% diethylether/hexanes)

Sources & evidence

ORD record
ord-ed587d3d7d0046bfaf5ba59dfeb97693
Source dataset
uspto-grants-2013_02
Patent number
US08367706B2

Reaction notes

Loading…