Morpholine → HCID 67107533, compound

HRID 1910836Notes

Reaction equation

HRID 1910836 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[C:10]3[N:15]([CH:16]=2)[CH:14]=[CH:13][CH:12]=[CH:11]3)=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[NH:23]1[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2N(C)C)CCCCC1>C1(C)C=CC=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl>[N:23]1([C:2]2[CH:7]=[CH:6][C:5]([C:8]3[CH:9]=[C:10]4[N:15]([CH:16]=3)[CH:14]=[CH:13][CH:12]=[CH:11]4)=[CH:4][CH:3]=2)[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1

Participants

7

Reactant 4

HCID 8083MorpholineHCID 10796Cesium carbonateHCID 3469402-(4-bromophenyl)indolizineHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenyl

Product 1

HCID 67107533HCID 67107533, compoundYield 24.4%

Reagents, catalysts & solvents 2

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 1140TolueneSolvent2×

Procedure

To 2-(4-bromo-phenyl)-indolizine (1.2 g, 4.42 mmol) in toluene (8 mL) was added cesium carbonate (4.3 g, 13.24 mmol) and morpholine (1.15 mL, 13.24 mmol). To this was added a mixture of bis-(triphenylphosphine)-palladium (II) chloride (120 mg) and 2-dicyclohexylphosphino-2′-(N,N′-dimethylamino)biphenyl (150 mg) in toluene (10 mL). The reaction mixture was degassed for 15 min and then refluxed for 16 h under an atmosphere of argon. The cooled reaction mixture was concentrated in vacuo and the residue dissolved in dichloromethane. The organic layer was washed with water and brine solution (×2), dried over sodium sulfate, filtered and concentrated. The crude compound was purified by column chromatography over silica gel (60-120 mesh) with 80% chloroform/petroleum ether to afford 2-(4-morpholin-4-yl-phenyl)-indolizine (300 mg, 24%) as a solid.

Workup

  1. additionTo this was added
  2. customThe reaction mixture was degassed for 15 min
  3. temperaturerefluxed for 16 h under an atmosphere of argon
  4. customThe cooled reaction mixture
  5. concentrationwas concentrated in vacuo
  6. dissolutionthe residue dissolved in dichloromethane
  7. washThe organic layer was washed with water and brine solution (×2)
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe crude compound was purified by column chromatography over silica gel (60-120 mesh) with 80% chloroform/petroleum ether

Sources & evidence

ORD record
ord-89f47e201e3749f4ad4bfbb95fd460c7
Source dataset
uspto-grants-2013_12
Patent number
US08604029B2

Reaction notes

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