Iodine → Methyl 2-(2-(3-bromo-4-fluorophenyl)acetyl)nicotinate

HRID 925082Notes

Reaction equation

HRID 925082 reaction equation
[Mg].[Br:2][C:3]1[CH:8]=[C:7]([CH2:9]Br)[CH:6]=[CH:5][C:4]=1[F:11].II.C[O:15][C:16]([C:18]1[C:23]([C:24]([O:26][CH3:27])=[O:25])=[CH:22][CH:21]=[CH:20][N:19]=1)=O>C(OCC)C.O1CCCC1>[Br:2][C:3]1[CH:8]=[C:7]([CH2:9][C:16]([C:18]2[N:19]=[CH:20][CH:21]=[CH:22][C:23]=2[C:24]([O:26][CH3:27])=[O:25])=[O:15])[CH:6]=[CH:5][C:4]=1[F:11]

Participants

7

Reactant 4

HCID 807IodineHCID 690582,3-Dimethyl 2,3-pyridinedicarboxylateHCID 5462224MagnesiumHCID 129227103-Bromo-4-fluorobenzyl Bromide

Product 1

HCID 69043835Methyl 2-(2-(3-bromo-4-fluorophenyl)acetyl)nicotinate

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of magnesium turnings (880 mg, 37 mmol) and 2-bromo-4-(bromomethyl)-1-fluorobenzene (1.0 g, 3.7 mmol) in anhydrous diethyl ether (15 ml) was treated with a piece of iodine. The mixture was then heated to gentle reflux until the color of the mixture disappeared, after which the heating continued for additional hour. The suspension was cooled to room temperature, and cannulated into a solution of dimethylpyridine-2,3-dicarboxylate (1.0 g, 5.1 mmol) in tetrahydrofuran (50 ml) at −78° C. The reaction mixture was maintained at the same temperature for 30 minutes, and was quenched with addition of water. After warming up to room temperature, the reaction mixture was partitioned between ethyl acetate and brine. The organic phase was washed with brine and concentrated. The residue was purified by flash chromatography (15% ethyl acetate in hexane) to provide the title compound. MS (DCI/NH3) m/z 353 (M+H)+.

Workup

  1. temperatureThe mixture was then heated
  2. temperatureto gentle reflux until the color of the mixture
  3. waitafter which the heating continued for additional hour
  4. temperatureThe reaction mixture was maintained at the same temperature for 30 minutes
  5. customwas quenched with addition of water
  6. temperatureAfter warming up to room temperature
  7. customthe reaction mixture was partitioned between ethyl acetate and brine
  8. washThe organic phase was washed with brine
  9. concentrationconcentrated
  10. customThe residue was purified by flash chromatography (15% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-d9a2ff35fd254f3d84b1433658bdc4ce
Source dataset
uspto-grants-2016_03
Patent number
US09283222B2

Reaction notes

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