Methyl anisate → 2-(4-Bromopyridin-2-yl)-1-(4-methoxyphenyl)ethanone

HRID 1475928Notes

Reaction equation

HRID 1475928 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([CH3:8])[CH:3]=1.[CH3:9][O:10][C:11]1[CH:20]=[CH:19][C:14]([C:15](OC)=[O:16])=[CH:13][CH:12]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[Cl-].[NH4+]>O1CCCC1.C(OCC)(=O)C>[Br:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([CH2:8][C:15]([C:14]2[CH:19]=[CH:20][C:11]([O:10][CH3:9])=[CH:12][CH:13]=2)=[O:16])[CH:3]=1

Participants

7

Reactant 4

HCID 8499Methyl anisateHCID 25517Ammonium ChlorideHCID 2733832Lithium HexamethyldisilazideHCID 27628354-Bromo-2-methylpyridine

Product 1

HCID 682760292-(4-Bromopyridin-2-yl)-1-(4-methoxyphenyl)ethanone

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of 4-bromo-2-methylpyridine (2.9 g, 16.8 mmol) and methyl 4-methoxybenzoate (2.8 g, 16.8 mmol) in tetrahydrofuran (42 mL) at 0° C. was added dropwise a 1M solution of lithium bis(trimethylsilyl)amide (33.6 mL, 33.6 mmol). The mixture was allowed to warm to room temperature and stirred for 3 days. A saturated solution of ammonium chloride (40 mL) was added and the mixture was diluted with ethyl acetate (50 mL). The separated aqueous layer was then extracted with ethyl acetate (3×25 mL). The combined organic layers were washed with brine, dried over anhydrous MgSO4, filtered and concentrated under reduced pressure to afford a residue which was purified by automated flash-chromatography (ethyl acetate/hexanes; 15/85). The title compound was obtained as a bright yellow solid (3.8 g, 75%). LCMS m/z 306.0; 308.0 (M+H)+, ret. time=2.48 min.

Workup

  1. extractionThe separated aqueous layer was then extracted with ethyl acetate (3×25 mL)
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over anhydrous MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customto afford a residue which
  7. customwas purified by automated flash-chromatography (ethyl acetate/hexanes; 15/85)

Sources & evidence

ORD record
ord-67295b1f4b5e4182a374e374eb9e92ee
Source dataset
uspto-grants-2015_04
Patent number
US09018395B2

Reaction notes

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