Triethylamine → 2-(2-(3-Methoxyphenyl)ethynyl)-5-methylpyridine

HRID 491409Notes

Reaction equation

HRID 491409 reaction equation
[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]#[C:9][Si](C)(C)C)=[N:6][CH:7]=1.Br[C:15]1[CH:16]=[C:17]([O:21][CH3:22])[CH:18]=[CH:19][CH:20]=1.CCN(CC)CC.[N+](CCCC)(CCCC)(CCCC)CCCC.[F-]>[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.O.CN(C)C=O>[CH3:22][O:21][C:17]1[CH:16]=[C:15]([C:9]#[C:8][C:5]2[CH:4]=[CH:3][C:2]([CH3:1])=[CH:7][N:6]=2)[CH:20]=[CH:19][CH:18]=1

Participants

9

Reactant 4

HCID 8471TriethylamineHCID 169713-BromoanisoleHCID 2724141Tetrabutylammonium FluorideHCID 447549315-Methyl-2-(2-(trimethylsilyl)ethynyl)pyridine

Product 1

HCID 160367622-(2-(3-Methoxyphenyl)ethynyl)-5-methylpyridineYield 52%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 5-methyl-2-trimethylsilanylethynylpyridine (5.32 mmol) in 25 mL degassed N,N-dimethylformamide was added successively 3-bromoanisole (6.96 mmol), CuI (0.57 mmol), Et3N (21.2 mmol) and trans-dichlorobis(triphenylphosphine)palladium (29 mmol). The resulting mixture was warmed to 70° C., Bu4NF (5.85 mmol) was added drop-wise, and the reaction was stirred at this temperature 2 h. After cooling, 20 mL of H2O was added and the resulting solution was extracted with EtOAc (4×20 mL). The organic layer was washed with saturated NaCl (3×20 mL), dried over Na2SO4 and evaporated to dryness. Purification of the residue by column chromatography provided M-5MPEP in 52% yield as a yellow oil. HCl salts were prepared by adding 2 M HCl/Et2O to a solution of free base in EtOAc and isolated by suction filtration. 1H NMR (CDC13) δ ppm: 2.20 (s, 3H, CH3); 3.67 (s, 3H, CH3); 6.79 (ddd, 1H, J=8.5, 2.5, 1.0 Hz, CHAr); 7.01-7.02 (m, 1H, CHAr); 7.07 (dt, 1H, J=8.5, 1.0 Hz, CHAr); 7.13 (t, IH, J=8.5 Hz, CHAr); 7.29 (d, 1H, J=7.5 Hz, CHAr); 7.33 (dd, 1H, J=7.5, 2.5 Hz, CHAr); 8.32 (s, 1H, CHAr). 13C NMR (CDCh) δ ppm: 18.8 (1C, CH3); 55.6 (1C, CH3); 88.8 (1C, C═C); 88.9 (1C, C═C); 115.9 (1C, CHAr); 116.9 (1C, CHAr); 123.8 (1C, Cq); 124.6 (1C, CHAr); 127.0 (1C, CHAr); 129.6 (1C, CHAr); 133.1 (1C, Cq); 137.0 (1C, CHAr); 140.8 (1C, Cq); 150.9 (1C, CHAr); 159.6 (1C, Cq). HCl salt mp 171-172° C. Anal. C 15H13NO HC1 0.2H20) C, H, N.

Workup

  1. temperatureAfter cooling
  2. extractionthe resulting solution was extracted with EtOAc (4×20 mL)
  3. washThe organic layer was washed with saturated NaCl (3×20 mL)
  4. dry with materialdried over Na2SO4
  5. customevaporated to dryness
  6. customPurification of the residue by column chromatography

Sources & evidence

ORD record
ord-c418efba449b40d0be798d9f874069c0
Source dataset
uspto-grants-2009_05
Patent number
US07531541B2

Reaction notes

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