Tri-o-tolylphosphine → HCID 18432761, compound

HRID 2305362Notes

Reaction equation

HRID 2305362 reaction equation
[F:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1I.[C:9]([O:13][C:14]([N:16]1[CH2:21][CH2:20][N:19]([C:22]([CH:24]2[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]2)=[O:23])[CH2:18][CH2:17]1)=[O:15])([CH3:12])([CH3:11])[CH3:10].CC(C)([O-])C.[Na+].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>O1CCOCC1.C(OCC)C.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:9]([O:13][C:14]([N:16]1[CH2:17][CH2:18][N:19]([C:22]([CH:24]2[CH2:29][CH2:28][N:27]([C:7]3[CH:6]=[CH:5][N:4]=[CH:3][C:2]=3[F:1])[CH2:26][CH2:25]2)=[O:23])[CH2:20][CH2:21]1)=[O:15])([CH3:12])([CH3:10])[CH3:11]

Participants

8

Reactant 4

HCID 80271Tri-o-tolylphosphineHCID 10803972Tert-butyl 4-(piperidine-4-carbonyl)piperazine-1-carboxylateHCID 109986363-Fluoro-4-IodopyridineHCID 23676156Sodium t-butoxide

Product 1

HCID 18432761HCID 18432761, compoundYield 35.6%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 3283Diethyl EtherSolventHCID 312751,4-DioxaneSolvent

Procedure

To a suspension of 3-fluoro-4-iodopyridine (2.23 g), 1-(tert-butoxycarbonyl)-4-(piperidin-4-ylcarbonyl) piperazine (1.49 g) and sodium t-butoxide (1.06 g) in 1,4-dioxan (20 ml) was added tris(dibenzylidene acetone)dipalladium(0) (0.09 g) and tri-o-tolylphosphine (0.12 g) and the mixture heated at reflux for 3 hours. The mixture was diluted with diethyl ether and washed with saturated aqueous sodium chloride solution. dried (Na2SO4) and evaporated. The residue was purified by chromatography on alumina (N32-63) eluting with 0.4% methanol in dichloromethane to give as a solid, 1-(tert-butoxycarbonyl)-4-[1-(3-fluoro-4-pyridyl)piperidin-4-ylcarbonyl]piperazine (0.70 g).

Workup

  1. temperaturethe mixture heated
  2. temperatureat reflux for 3 hours
  3. washwashed with saturated aqueous sodium chloride solution
  4. dry with materialdried (Na2SO4)
  5. customevaporated
  6. customThe residue was purified by chromatography on alumina (N32-63)
  7. washeluting with 0.4% methanol in dichloromethane

Sources & evidence

ORD record
ord-f7d5c3c7bd6647a3aea96ffe48a15aa7
Source dataset
uspto-grants-2002_08
Patent number
US06440972B1

Reaction notes

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