4-Methoxypiperidine → HCID 59327226, compound

HRID 1880041Notes

Reaction equation

HRID 1880041 reaction equation
Br[C:2]1[C:3]([Cl:8])=[N:4][CH:5]=[CH:6][CH:7]=1.[CH3:9][O:10][CH:11]1[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1.CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.CC(C)([O-])C.[Na+]>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]>[Cl:8][C:3]1[C:2]([N:14]2[CH2:15][CH2:16][CH:11]([O:10][CH3:9])[CH2:12][CH2:13]2)=[CH:7][CH:6]=[CH:5][N:4]=1

Participants

7

Reactant 4

HCID 776664-MethoxypiperidineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 6933243-Bromo-2-chloropyridineHCID 23676156Sodium t-butoxide

Product 1

HCID 59327226HCID 59327226, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A round-bottomed flask was charged with 3-bromo-2-chloropyridine (620 mg, 3.22 mmol), 4-methoxy-piperidine (371 mg, 3.22 mmol), tris(dibenzylideneacetone)dipalladium(0) (147 mg, 0.161 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (186 mg, 0.322 mmol), and sodium tert-butoxide (464 mg, 4.83 mmol) in toluene (6442 μL), sealed and then sparged with argon for 5 min. The reaction mixture was heated at 100° C. with stirring for 2 h. After cooling to RT, the reaction mixture was filtered through a pad of celite and purified by chromatography through a Redi-Sep pre-packed silica gel column (40 g), eluting with a gradient of 0% to 40% EtOAc in hexane, to provide 2-chloro-3-(4-methoxypiperidin-1-yl) as orange oil. MS (ESI, pos. ion) m/z: 226.8 (M+1).

Workup

  1. customsealed
  2. customsparged with argon for 5 min
  3. temperatureAfter cooling to RT
  4. filtrationthe reaction mixture was filtered through a pad of celite
  5. custompurified by chromatography through a Redi-Sep pre-packed silica gel column (40 g)
  6. washeluting with a gradient of 0% to 40% EtOAc in hexane
  7. customto provide 2-chloro-3-(4-methoxypiperidin-1-yl) as orange oil

Sources & evidence

ORD record
ord-4ce687193c314950acc928afaaa3b96f
Source dataset
uspto-grants-2012_11
Patent number
US08318718B2

Reaction notes

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