Tri-o-tolylphosphine → 1-(t-Butoxycarbonyl)-4-[1-(3-fluoro-4-pyridyl)piperazin-4-ylcarbonyl]piperazine

HRID 2305367Notes

Reaction equation

HRID 2305367 reaction equation
C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.[F:23][C:24]1[CH:25]=[N:26][CH:27]=[CH:28][C:29]=1I.[C:31]([O:35][C:36]([N:38]1[CH2:43][CH2:42][N:41]([C:44]([N:46]2[CH2:51][CH2:50][NH:49][CH2:48][CH2:47]2)=[O:45])[CH2:40][CH2:39]1)=[O:37])([CH3:34])([CH3:33])[CH3:32].CC(C)([O-])C.[Na+]>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:31]([O:35][C:36]([N:38]1[CH2:43][CH2:42][N:41]([C:44]([N:46]2[CH2:51][CH2:50][N:49]([C:29]3[CH:28]=[CH:27][N:26]=[CH:25][C:24]=3[F:23])[CH2:48][CH2:47]2)=[O:45])[CH2:40][CH2:39]1)=[O:37])([CH3:34])([CH3:32])[CH3:33]

Participants

8

Reactant 4

HCID 80271Tri-o-tolylphosphineHCID 109986363-Fluoro-4-IodopyridineHCID 18432746Tert-butyl 4-(piperazine-1-carbonyl)piperazine-1-carboxylateHCID 23676156Sodium t-butoxide

Product 1

HCID 184327591-(t-Butoxycarbonyl)-4-[1-(3-fluoro-4-pyridyl)piperazin-4-ylcarbonyl]piperazineYield 43%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
100 °C

Procedure

Tris(dibenzylideneacetone)dipalladium(0) (0.184 g) and tri-o-tolylphosphine (0.244 g) were added to a suspension of 3-fluoro-4-iodopyridine (4.46 g), 1-[1-(t-butoxycarbonyl)piperazin-4-ylcarbonyl]piperazine (3.0 g) and sodium t-butoxide (2.12 g) in dry 1,4-dioxane (40 ml) under an atmosphere of argon. The mixture was heated at 100° C. for 18 hours. The mixture was cooled, diluted with diethyl ether (200 ml) and washed with saturated brine (40 ml). The aqueous layer was back-extracted with diethyl ether (2×100 ml). The ether layers were all combined, washed with saturated brine (2×100 ml), dried (Na2SO4) and evaporated. The residual oil was purified by chromatography on alumina (N32-63) using 0.1-0.4% methanol in dichloromethane as eluent to give 1-(t-butoxycarbonyl)-4-[1-(3-fluoro-4-pyridyl)piperazin-4-ylcarbonyl]piperazine (1.7 g) as an orange solid: NMR (CDCl3): 1.47 (s, 9H), 3.25 (m, 8H), 3.45 (m, 8H), 6.75 (dd, 1H), 8.20 (dd, 2H); m/z 394 (M+1).

Workup

  1. temperatureThe mixture was cooled
  2. washwashed with saturated brine (40 ml)
  3. extractionThe aqueous layer was back-extracted with diethyl ether (2×100 ml)
  4. washwashed with saturated brine (2×100 ml)
  5. dry with materialdried (Na2SO4)
  6. customevaporated
  7. customThe residual oil was purified by chromatography on alumina (N32-63)

Sources & evidence

ORD record
ord-7ab330ba7a284a37996217c689bf1645
Source dataset
uspto-grants-2002_08
Patent number
US06440972B1

Reaction notes

Loading…