Piperidine → HCID 58307082, compound

HRID 1909893Notes

Reaction equation

HRID 1909893 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([CH2:8][N:9]2[C:17]3[C:12](=[CH:13][C:14]([Cl:23])=[CH:15][C:16]=3[C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH:11]=[CH:10]2)=[N:6][CH:7]=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+].[NH:72]1[CH2:77][CH2:76][CH2:75][CH2:74][CH2:73]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].C1(C)C=CC=CC=1>[Cl:23][C:14]1[CH:13]=[C:12]2[C:17](=[C:16]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH:15]=1)[N:9]([CH2:8][C:5]1[CH:4]=[CH:3][C:2]([N:72]3[CH2:77][CH2:76][CH2:75][CH2:74][CH2:73]3)=[CH:7][N:6]=1)[CH:10]=[CH:11]2

Participants

7

Reactant 4

HCID 8082PiperidineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 23676156Sodium t-butoxideHCID 58306512HCID 58306512, compound

Product 1

HCID 58307082HCID 58307082, compoundYield 75.9%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of ethyl 1-[(5-bromopyridin-2-yl)methyl]-5-chloro-1H-indole-7-carboxylate (0.30 g), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (88 mg), sodium tert-butoxide (0.12 g), piperidine (84 mg), tris(dibenzylideneacetone)dipalladium (0) (70 mg), and dehydrated toluene (6.0 mL) was bubbled with argon for 10 minutes, followed by stirring at 110° C. for 2 hours. The reaction mixture was filtered through Celite and washed with diethyl ether. To this filtrate was added saturated aqueous sodium bicarbonate, followed by extraction with diethyl ether, and the organic layer was washed with saturated brine. After drying over anhydrous sodium sulfate, filtering and concentrating under reduced pressure, the residue was purified by silica gel column chromatography (hexane/ethyl acetate=1/1) to obtain ethyl 5-chloro-1-[(5-piperidin-1-ylpyridin-2-yl)methyl]-1H-indole-7-carboxylate (0.23 g).

Workup

  1. customwas bubbled with argon for 10 minutes
  2. filtrationThe reaction mixture was filtered through Celite
  3. washwashed with diethyl ether
  4. additionTo this filtrate was added saturated aqueous sodium bicarbonate
  5. extractionfollowed by extraction with diethyl ether
  6. washthe organic layer was washed with saturated brine
  7. dry with materialAfter drying over anhydrous sodium sulfate
  8. filtrationfiltering
  9. concentrationconcentrating under reduced pressure
  10. customthe residue was purified by silica gel column chromatography (hexane/ethyl acetate=1/1)

Sources & evidence

ORD record
ord-d3a840e92c544e21b45490173b72db17
Source dataset
uspto-grants-2013_12
Patent number
US08598355B2

Reaction notes

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