Acetonitrile → 5-Bromo-2-(3-fluorophenyl)-4-methoxypyridine

HRID 1504370Notes

Reaction equation

HRID 1504370 reaction equation
CC#N.[F:4][C:5]1[CH:6]=[C:7]([C:11]2[CH:16]=[C:15]([O:17][CH3:18])[CH:14]=[CH:13][N:12]=2)[CH:8]=[CH:9][CH:10]=1.[Br:19]N1C(=O)CCC1=O.CCOC(C)=O>[Al]>[Br:19][C:14]1[C:15]([O:17][CH3:18])=[CH:16][C:11]([C:7]2[CH:8]=[CH:9][CH:10]=[C:5]([F:4])[CH:6]=2)=[N:12][CH:13]=1

Participants

6

Reactant 4

HCID 6342AcetonitrileHCID 8857Ethyl AcetateHCID 67184N-bromobutanimideHCID 463129782-(3-Fluorophenyl)-4-methoxypyridine

Product 1

HCID 1177372915-Bromo-2-(3-fluorophenyl)-4-methoxypyridineYield 13.7%

Reagents, catalysts & solvents 1

HCID 5359268AluminumSolvent

Conditions

Temperature
55 °C

Procedure

A MeCN (22 mL) solution of 2-(3-fluorophenyl)-4-methoxypyridine (2.21 g, 10.88 mmol) and N-bromosuccinimide (2.129 g, 11.96 mmol) in a 40-mL vial was wrapped in aluminum foil and stirred at 55° C. overnight. 22 h later, the reaction was cooled to rt, quenched with 1:1 sat. aq. NaHCO3:sat. aq. Na2S2O3 and extracted thrice with EtOAc. The organic extracts were combined, washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo to a brown oil. Column chromatography (50 g Snap Ultra column, 15% to 100% EtOAc/hept) afforded 5-bromo-2-(3-fluorophenyl)-4-methoxypyridine (0.420 g, 1.489 mmol, 13.69% yield) as a white amorphous solid. m/z (ESI) 282.0 (M+H)+.

Workup

  1. temperature22 h later, the reaction was cooled to rt
  2. customquenched with 1:1 sat. aq. NaHCO3
  3. extractionaq. Na2S2O3 and extracted thrice with EtOAc
  4. washwashed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo to a brown oil

Sources & evidence

ORD record
ord-b0cc6b66fd3a4854b1a4ae7e9f706d51
Source dataset
uspto-grants-2015_12
Patent number
US09212182B2

Reaction notes

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