1-Bromo-3,5-difluorobenzene → 2-{4-[3-(3,5-Difluorophenyl)prop-2-ynylidene]piperidin-1-yl}-6-methyl-3-nitropyridine

HRID 1896029Notes

Reaction equation

HRID 1896029 reaction equation
[CH3:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][C:11](=[CH:14][C:15]#[CH:16])[CH2:10][CH2:9]2)[C:5]([N+:17]([O-:19])=[O:18])=[CH:4][CH:3]=1.O.O.O.C([O-])(=O)C.[Na+].Br[C:29]1[CH:34]=[C:33]([F:35])[CH:32]=[C:31]([F:36])[CH:30]=1>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:35][C:33]1[CH:34]=[C:29]([C:16]#[C:15][CH:14]=[C:11]2[CH2:12][CH2:13][N:8]([C:6]3[C:5]([N+:17]([O-:19])=[O:18])=[CH:4][CH:3]=[C:2]([CH3:1])[N:7]=3)[CH2:9][CH2:10]2)[CH:30]=[C:31]([F:36])[CH:32]=1

Participants

6

Reactant 3

HCID 1363131-Bromo-3,5-difluorobenzeneHCID 23665404Sodium Acetate TrihydrateHCID 866273496-Methyl-3-Nitro-2-(4-prop-2-ynylidenepiperidin-1-yl)pyridine

Product 1

HCID 251819152-{4-[3-(3,5-Difluorophenyl)prop-2-ynylidene]piperidin-1-yl}-6-methyl-3-nitropyridineYield 74.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

To a suspension of Compound 274c (70 mg, 0.27 mmol), sodium acetate trihydrate (74.2 mg, 0.55 mmol) and 1-bromo-3,5-difluorobenzene (33.5 μl, 0.27 mmol) in 2.05 mL of DMF flushed with nitrogen was added tetrakis(triphenylphosphine)palladium(0) (15.8 mg, 0.014 mmol) and the reaction mixture was put into a microwave oven (Biotage) at 120° C. for 10 min. Dilution with EtOAc, washing with H2O and drying over Na2SO4 followed by evaporation and purification of the residue by automated flash liquid chromatography (Horizon™-Biotage) (PE-CH2Cl2 6:4) afforded 74 mg (73.7%) of the title compound.

Workup

  1. customflushed with nitrogen
  2. customthe reaction mixture was put into a microwave oven
  3. washDilution with EtOAc, washing with H2O
  4. dry with materialdrying over Na2SO4
  5. customfollowed by evaporation and purification of the residue by automated flash liquid chromatography (Horizon™-Biotage) (PE-CH2Cl2 6:4)

Sources & evidence

ORD record
ord-71a32cef498c4767ae11697b8324abc9
Source dataset
uspto-grants-2013_08
Patent number
US08518916B2

Reaction notes

Loading…