4-Iodophenol → 6-(4-Iodo-phenoxymethyl)-pyridine-2-carboxylic acid ethyl ester

HRID 2112996Notes

Reaction equation

HRID 2112996 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([CH2:12]Br)[N:7]=1)=[O:5])[CH3:2].[I:14][C:15]1[CH:20]=[CH:19][C:18]([OH:21])=[CH:17][CH:16]=1.C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[CH2:1]([O:3][C:4]([C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([CH2:12][O:21][C:18]2[CH:19]=[CH:20][C:15]([I:14])=[CH:16][CH:17]=2)[N:7]=1)=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 108944-IodophenolHCID 11430Potassium CarbonateHCID 23033755Ethyl 6-(bromomethyl)picolinate

Product 1

HCID 576433526-(4-Iodo-phenoxymethyl)-pyridine-2-carboxylic acid ethyl esterYield 75%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

6-Bromomethyl-pyridine-2-carboxylic acid ethyl ester (1:1.72 g, 48 mmol; from Step 1 above) was dissolved in acetone (250 mL) and 4-iodophenol (11.61 g, 52.8 mmol; available from Aldrich Chemical Company, Inc., Milwaukee, Wis.) was added, followed by potassium carbonate (7.55 g, 54.6 mmol). The mixture was heated overnight at 65 degrees, and it was then cooled and filtered. The solid was washed with small portions of acetone and the filtrate was concentrated to approximately 100 mL by evaporation. The solution was warmed and then diluted with water (approximately 70 mL). The resulting brown solution was cloudy and started to precipitate an oily solid. The mixture was scratched with a spatula and allowed to cool to room temperature. The off-white precipitate was filtered off, washed with several portions of acetone/water (1:1), and then dried in vacuo over phosphorus pentoxide to give 6-(4-iodo-phenoxymethyl)-pyridine-2-carboxylic acid ethyl ester (13.72 g, 75%) as an off-white crystalline solid. MS (MH+) 384. 1HNMR (CDCl3): δ 1.47 (t, 3H, J=7 Hz), 4.52 (q, 2H, J=7 Hz), 5.33 (s, 2H), 6.78 (d, 2H, J=9 Hz), 7.58 (d, 2H, J=9 Hz), 7.74 (d, 1H, J=7.8 Hz), 7.91 (dd, 1H, J=7.8, 7.8 Hz), 8.09 (d, 1H, J=7.8 Hz).

Workup

  1. temperatureThe mixture was heated overnight at 65 degrees
  2. temperatureit was then cooled
  3. filtrationfiltered
  4. washThe solid was washed with small portions of acetone
  5. concentrationthe filtrate was concentrated to approximately 100 mL by evaporation
  6. temperatureThe solution was warmed
  7. additiondiluted with water (approximately 70 mL)
  8. customto precipitate an oily solid
  9. filtrationThe off-white precipitate was filtered off
  10. washwashed with several portions of acetone/water (1:1)
  11. dry with materialdried in vacuo over phosphorus pentoxide

Sources & evidence

ORD record
ord-31a4b0b117834717b6b6b09e0040a5d3
Source dataset
uspto-grants-2009_04
Patent number
US07524870B2

Reaction notes

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