2-Bromopyridine → (5-Bromo-2-fluorophenyl)(pyridin-2-yl)methanone

HRID 879421Notes

Reaction equation

HRID 879421 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.C([Mg]Cl)(C)C.[Br:13][C:14]1[CH:15]=[CH:16][C:17]([F:26])=[C:18]([CH:25]=1)[C:19](N(OC)C)=[O:20]>O1CCCC1>[Br:13][C:14]1[CH:15]=[CH:16][C:17]([F:26])=[C:18]([C:19]([C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=2)=[O:20])[CH:25]=1

Participants

5

Reactant 3

HCID 79732-BromopyridineHCID 606295205-bromo-2-fluoro-N-methoxy-N-methylbenzamideHCID 178418918HCID 178418918, compound

Product 1

HCID 79018065(5-Bromo-2-fluorophenyl)(pyridin-2-yl)methanone

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

An oven-dried flask was cooled under argon, then charged with anhydrous THF (40 mL) and 2-bromopyridine (1.76 mL, 18 mmol). Isopropylmagnesium chloride in tetrahydrofuran (2.0 M in THF, 11 mL) was then added dropwise at room temperature. The mixture was then stirred at room temperature for 2 hours, then cooled to 0° C., whereupon a THF solution (5 mL) of 5-bromo-2-fluoro-N-methoxy-N-methylbenzamide (3.93 g, 15 mmol) was added. The mixture was then allowed to warm to room temperature and stirred for 2 hours. The reaction was quenched with saturated NH4Cl, extracted with EtOAc, washed with 10% HCl, dried over Na2SO4, and purified by column chromatography (gradient 0 to 10% EtOAc/hexanes) to afford the product. 1H NMR (400 MHz, CDCl3) δ 8.69 (d, J=4.6 Hz, 1H), 8.09 (d, J=7.8 Hz, 1H), 7.92 (t, J=7.7 Hz, 1H), 7.79 (dd, J=5.8, 1.4 Hz, 1H), 7.67-7.59 (m, 1H), 7.52 (dd, J=7.4, 4.9 Hz, 1H), 7.04 (t, J=9.0 Hz, 1H).

Workup

  1. temperatureAn oven-dried flask was cooled under argon
  2. additionwas added
  3. temperatureto warm to room temperature
  4. stirringstirred for 2 hours
  5. customThe reaction was quenched with saturated NH4Cl
  6. extractionextracted with EtOAc
  7. washwashed with 10% HCl
  8. dry with materialdried over Na2SO4
  9. custompurified by column chromatography (gradient 0 to 10% EtOAc/hexanes)
  10. customto afford the product

Sources & evidence

ORD record
ord-9e6962b4d8844453aed679487cbcff5e
Source dataset
uspto-grants-2015_03
Patent number
US08987250B2

Reaction notes

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