Tetrahydrofuran → Dibenzylidene acetone

HRID 1180218Notes

Reaction equation

HRID 1180218 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1.[F:8][C:9]1[CH:14]=[CH:13][C:12]([N+:15]([O-:17])=[O:16])=[CH:11][C:10]=1B1OC(C)(C)C(C)(C)O1.[F-].[K+].[C:29](P(C(C)(C)C)C(C)(C)C)(C)([CH3:31])[CH3:30].[CH2:42]1[CH2:46][O:45][CH2:44][CH2:43]1>O.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]>[F:8][C:9]1[CH:14]=[CH:13][C:12]([N+:15]([O-:17])=[O:16])=[CH:11][C:10]=1[C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1.[CH:2](=[CH:3][C:44]([CH:43]=[CH:42][C:46]1[CH:13]=[CH:14][CH:9]=[CH:10][CH:11]=1)=[O:45])[C:7]1[CH:31]=[CH:29][CH:30]=[CH:5][CH:6]=1

Participants

9

Reactant 5

HCID 8028TetrahydrofuranHCID 122863-BromopyridineHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 522689Potassium FluorideHCID 38332972-Fluoro-5-nitrophenylboronic acid, pinacol ester

Product 2

HCID 95417Dibenzylidene acetoneHCID 179648273-(2-Fluoro-5-nitrophenyl)pyridine

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolvent

Procedure

A slurry of 3-bromopyridine (19 g, 120 mmol), 2-(2-fluoro-5-nitrophenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (40 g, 150 mmol) and KF (23 g, 396 mmol) in THF (600 ml) and water (30 ml) was degassed with nitrogen for 10 min, then treated with tris(dibenzylideneacetone)-dipalladium(0) (2.2 g, 2.4 mmol) followed by tri-tert-butylphosphine (0.2 M solution in 1,4-dioxane; 2.4 ml, 0.48 mmol), and the reaction was stirred mechanically at ambient temperature for 30 min. The mixture was then heated at 50° C. for 1 h before being cooled to ambient temperature. The reaction was poured into ice-cold 0.5 N aqueous NaOH solution and stirred for 1 h. The solid product was collected by filtration, washed with water, allowed to dry under suction, then washed with isohexane and dried to give 3-(2-fluoro-5-nitrophenyl)pyridine as a grey solid (26.2 g, contaminated with dibenzylideneacetone): δH (400 MHz, CDCl3) 7.37 (1H, t, J 9), 7.45 (1H, ddd, J 8, 5 and 1), 7.89-7.93 (1H, m), 8.28-8.33 (1H, m), 8.40 (1H, dd, J 7 and 3), 8.71 (1H, d, J 4), 8.84 (1H, s).

Workup

  1. temperatureThe mixture was then heated at 50° C. for 1 h
  2. temperaturebefore being cooled to ambient temperature
  3. stirringstirred for 1 h
  4. filtrationThe solid product was collected by filtration
  5. washwashed with water
  6. customto dry under suction
  7. washwashed with isohexane
  8. customdried

Sources & evidence

ORD record
ord-54c3e1777dac4a208703be600720c163
Source dataset
uspto-grants-2007_10
Patent number
US07279580B2

Reaction notes

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