3-Iodophenol → Ethyl 2-(4-((3-hydroxyphenyl)ethynyl)phenoxy)acetate

HRID 2042990Notes

Reaction equation

HRID 2042990 reaction equation
[C:1]([C:3]1[CH:15]=[CH:14][C:6]([O:7][CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])=[CH:5][CH:4]=1)#[CH:2].I[C:17]1[CH:18]=[C:19]([OH:23])[CH:20]=[CH:21][CH:22]=1.CCN(C(C)C)C(C)C.[Cl-].[NH4+]>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.[Cu]I.O.CN(C=O)C>[OH:23][C:19]1[CH:18]=[C:17]([C:2]#[C:1][C:3]2[CH:15]=[CH:14][C:6]([O:7][CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])=[CH:5][CH:4]=2)[CH:22]=[CH:21][CH:20]=1

Participants

9

Reactant 4

HCID 122723-IodophenolHCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 22450859Ethyl 2-(4-ethynylphenoxy)acetate

Product 1

HCID 25149897Ethyl 2-(4-((3-hydroxyphenyl)ethynyl)phenoxy)acetate

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a dried Schlenk flask filled with nitrogen was added Pd(PPh3)4 (17.3 mg, 0.015 mmol), CuI (6.6 mg, 0.035 mmol), ethyl 2-(4-ethynylphenoxy)acetate (60.6 mg, 0.294 mmol), and 3-iodophenol (78.4 mg, 0.352 mmol) was added. The flask was evacuated, equipped with a septum, and filled with nitrogen. DMF (5 mL) and DIPEA (0.1 mL, 0.6 mmol) were added through the septum. The reaction was stirred over night and was neutralized with saturated aqueous ammonium chloride (5 mL). Water (5 mL) was added and the mixture was extracted with EtOAc (3×10 mL). The combined EtOAc phases was washed with brine, dried over MgSO4, and concentrated under reduced pressure. The product was purified on a dry silica column (EtOAc:hexanes 1:90→90:1 v/v). The final product was yellow/orange and solid (52 mg, 60%). Rf=0.46 (EtOAc:hexanes 1:1 v/v). 1H-NMR (DMSO-d6): □ 1.22 (t, 3H, J=7.7 Hz, CH2CH3); 4.18 (q, 2H, J=7.5 Hz, CH2CH3); 4.84 (s, 2H, OCH2); 6.9 (m, 5H, Ph); 7.20 (t, 1H, J=8.0 Hz, Ph); 7.49 (m, 2H, Ph); 9.67 (s, 1H, OH). 13C-NMR (DMSO-d6): □ 14.0 (CH2CH3); 60.7 (CH2CH3); 64.7 (OCH2); 88.3 (CC); 88.6 (CC); 115.0, 116.0, 117.6, 122.1, 123.4, 128.4, 129.8, 132.9, 157.3, 157.8 (Ph); 168.5 (COO).

Workup

  1. additionTo a dried Schlenk flask filled with nitrogen
  2. additionwas added
  3. customThe flask was evacuated
  4. customequipped with a septum
  5. additionfilled with nitrogen
  6. extractionthe mixture was extracted with EtOAc (3×10 mL)
  7. washThe combined EtOAc phases was washed with brine
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated under reduced pressure
  10. customThe product was purified on a dry silica column (EtOAc:hexanes 1:90→90:1 v/v)

Sources & evidence

ORD record
ord-bd18884013bc40a3ac02d457497f1566
Source dataset
uspto-grants-2013_11
Patent number
US08586607B2

Reaction notes

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