Diisopropylethylamine → 2-Chloro-5-((2-chlorophenyl)ethynyl)isonicotinaldehyde

HRID 1502366Notes

Reaction equation

HRID 1502366 reaction equation
Br[C:2]1[C:7]([CH:8]=[O:9])=[CH:6][C:5]([Cl:10])=[N:4][CH:3]=1.[Cl:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[C:18]#[CH:19].C(N(CC)C(C)C)(C)C>O1CCOCC1.C(OCC)(=O)C.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:10][C:5]1[CH:6]=[C:7]([C:2]([C:19]#[C:18][C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=2[Cl:11])=[CH:3][N:4]=1)[CH:8]=[O:9]

Participants

8

Reactant 3

HCID 81531DiisopropylethylamineHCID 5859951-Chloro-2-ethynylbenzeneHCID 534183815-Bromo-2-chloropyridine-4-carbaldehyde

Product 1

HCID 866749492-Chloro-5-((2-chlorophenyl)ethynyl)isonicotinaldehydeYield 88.5%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of 5-bromo-2-chloroisonicotinaldehyde (1.0 g, 4.5 mmol), 1-chloro-2-ethynylbenzene (650 mg, 4.7 mmol), N,N-diisopropylethylamine (1.6 mL, 9.1 mmol), copper(I) iodide (43 mg, 0.23 mmol), and bis(triphenylphosphine)palladium(II) chloride (159 mg, 0.23 mmol) in 1,4-dioxane (21 mL) was heated at 50° C. for 1 hour. The cooled reaction mixture was diluted with ethyl acetate (100 mL) and washed with water (100 mL). The organic layer was separated, dried over sodium sulfate, filtered, and evaporated in vacuo to afford a residue that was purified by flash chromatography (silica, 40 g, ISCO, 0-30% ethyl acetate in heptane) to afford the title compound as an off-white solid (1.1 g, 88%). 1H NMR (400 MHz, CDCl3) δ 10.64 (s, 1H), 8.77 (s, 1H), 7.77 (s, 1H), 7.62 (dd, J=7.5, 1.7 Hz, 1H), 7.49 (d, J=7.9 Hz, 1H), 7.38 (td, J=7.8, 1.8 Hz, 1H), 7.32 (td, J=7.5, 1.2 Hz, 1H).

Workup

  1. customThe cooled reaction mixture
  2. washwashed with water (100 mL)
  3. customThe organic layer was separated
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customto afford a residue that
  8. customwas purified by flash chromatography (silica, 40 g, ISCO, 0-30% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-e7502bacfdaa4683b2a63bdeec140218
Source dataset
uspto-grants-2015_12
Patent number
US09206175B2

Reaction notes

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