4-Bromophenol → 4-[2-(4-Bromophenoxy)ethyl]pyridine

HRID 1475852Notes

Reaction equation

HRID 1475852 reaction equation
N(C(OCC)=O)=NC(OCC)=O.[N:13]1[CH:18]=[CH:17][C:16]([CH2:19][CH2:20][OH:21])=[CH:15][CH:14]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Br:41][C:42]1[CH:47]=[CH:46][C:45](O)=[CH:44][CH:43]=1>C1COCC1>[Br:41][C:42]1[CH:47]=[CH:46][C:45]([O:21][CH2:20][CH2:19][C:16]2[CH:17]=[CH:18][N:13]=[CH:14][CH:15]=2)=[CH:44][CH:43]=1

Participants

6

Reactant 4

HCID 78084-BromophenolHCID 11776TriphenylphosphineHCID 729214-PyridineethanolHCID 220568ethyl N-ethoxycarbonyliminocarbamate

Product 1

HCID 608918714-[2-(4-Bromophenoxy)ethyl]pyridineYield 53.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Diethyl azodicarboxylate (4.44 mL, mmol, 40%) was slowly added to a solution of 2-pyridin-4-yl-ethanol (1.00 g, 8.12 mmol), triphenylphosphine (2.56 g, 9.74 mmol), and 4-bromophenol (1.40 g, 8.12 mmol) in THF (40.6 mL) at 0° C. under nitrogen. The reaction was allowed to warm to room temperature and stirred overnight. The reaction mixture was quenched with water (150 mL) and extracted with ethyl acetate (200 mL). The organics were washed with 1N aqueous NaOH (100 mL) and brine (100 mL). The organics were dried (Na2SO4), filtered, and concentrated. The crude material was crystallized with ether:heptanes (1:1, ˜25 mL) and the solid was removed via filtration and washed with ether:heptanes. The combined filtrates were concentrated and further purified via flash chromatography using an Analogix SF25-40 g column and ethyl acetate in heptane (0-30%) as the eluant to afford the title compound as a clear liquid (1.20 g, 46.2%). LC-MS m/z 278.4 (M+1). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 3.11 (t, 2H) 4.19 (t, J=6.44 Hz, 2H) 6.77 (d, J=8.98 Hz, 2H) 7.22-7.26 (m, 2H) 7.38 (d, J=4.69 Hz, 2H) 8.54-8.57 (m, 3H)

Workup

  1. customThe reaction mixture was quenched with water (150 mL)
  2. extractionextracted with ethyl acetate (200 mL)
  3. washThe organics were washed with 1N aqueous NaOH (100 mL) and brine (100 mL)
  4. dry with materialThe organics were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude material was crystallized with ether:heptanes (1:1, ˜25 mL)
  8. customthe solid was removed via filtration
  9. washwashed with ether
  10. concentrationThe combined filtrates were concentrated
  11. customfurther purified via flash chromatography

Sources & evidence

ORD record
ord-aee19749192f46f78fea9fdace08c16b
Source dataset
uspto-grants-2015_04
Patent number
US09018384B2

Reaction notes

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