2-Chloropyridine → HCID 66703932, compound

HRID 424424Notes

Reaction equation

HRID 424424 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[O:13][CH2:12][CH2:11][N:10]([C@@H:14]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH3:15])[CH2:9]2)=[CH:4][CH:3]=1.Cl[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=1.CC(C)([O-])C.[K+].[Cl-].C(C1C=CC=C(C(C)C)C=1[N+]1C=CN(C2C(C(C)C)=CC=CC=2C(C)C)C=1)(C)C>O1CCOCC1.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]>[C:16]1([C@H:14]([N:10]2[CH2:11][CH2:12][O:13][C@@H:8]([C:5]3[CH:4]=[CH:3][C:2]([NH:1][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=4)=[CH:7][CH:6]=3)[CH2:9]2)[CH3:15])[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1

Participants

7

Reactant 4

HCID 79772-ChloropyridineHCID 27349131,3-Bis(2,6-diisopropylphenyl)imidazolium chlorideHCID 23665647Potassium tert-butoxideHCID 66594463HCID 66594463, compound

Product 1

HCID 66703932HCID 66703932, compoundYield 36%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

A solution of (2S)-2-(4-aminophenyl)-4-((1R)-1-phenylethyl)morpholine (1.5 g, 5.31 mmol), 2-chloropyridine (1.21 g, 10.6 mmol), tris(dibenzylideneacetone)-dipalladium(0) (52.6 mg, 0.05 mmol), potassium tert-butoxide (0.88 g, 7.8 mmol) and 1,3-bis(2,6-di-i-propylphenyl)imidazolium chloride (89.6 mg, 0.21 mmol) in dioxane (17 ml) was stirred at 90° C. for 15 hours. The solvent was removed under reduced pressure and the residue was partitioned between water and ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and the solvent was evaporated under reduced pressure. The resulting residue was purified by column chromatography on silica gel (hexane-ethyl acetate, 1:2) to afford N-(4-((2S)-4-((1R)-1-Phenylethyl)-morpholin-2-yl)phenyl)pyridin-2-amine (0.68 g, 36%) as red crystals.

Workup

  1. customThe solvent was removed under reduced pressure
  2. customthe residue was partitioned between water and ethyl acetate
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. customThe resulting residue was purified by column chromatography on silica gel (hexane-ethyl acetate, 1:2)

Sources & evidence

ORD record
ord-29942f8da85f492689880a7fb5270072
Source dataset
uspto-grants-2012_01
Patent number
US08106045B2

Reaction notes

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