Benzoic acid, 4-fluoro-, ethyl ester → 2-(4-Chloropyridin-2-yl)-1-(4-fluorophenyl)ethan-1-one

HRID 723983Notes

Reaction equation

HRID 723983 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([CH3:8])[CH:3]=1.[F:9][C:10]1[CH:20]=[CH:19][C:13]([C:14](OCC)=[O:15])=[CH:12][CH:11]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>O1CCCC1>[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([CH2:8][C:14]([C:13]2[CH:19]=[CH:20][C:10]([F:9])=[CH:11][CH:12]=2)=[O:15])[CH:3]=1

Participants

5

Reactant 3

HCID 67976Benzoic acid, 4-fluoro-, ethyl esterHCID 5813924-Chloro-2-methylpyridineHCID 2733832Lithium Hexamethyldisilazide

Product 1

HCID 218740612-(4-Chloropyridin-2-yl)-1-(4-fluorophenyl)ethan-1-oneYield 99%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a cold (020 C.) solution of 4-chloro-2-picoline (5.0 g, 39 mmol) and ethyl 4-fluorobenzoate (6.6 g, 39 mmol) in tetrahydrofuran (100 mL) was added lithium bis(trimethylsilyl)amide (80 mL, 1.0 M in tetrahydrofuran, 80 mmol) dropwise via a pressure equalizing funnel over 30 minutes. Upon complete addition, the cold bath was removed and the resulting solution was stirred at room temperature for 15 hours. The reaction mixture was concentrated under reduced pressure and methanol was added to the reaction, resulting in the formation of a white precipitate. The precipitate was collected by filtration and dried to give 2-(4-chloro-2-pyridinyl)-1-(4-fluorophenyl)ethanone (9.6 g, 99%) as a white solid. 1H-NMR (DMSO-d6): δ 7.90 (m, 3H), 7.11 (t, 2H), 6.56 (s, 1H), 5.67 (s, 1H), 4.14 (m, 2H); 19F-NMR (DMSO-d6): δ −115.67; MS m/z 250 (M+1).

Workup

  1. customover 30 minutes
  2. additionUpon complete addition
  3. customthe cold bath was removed
  4. concentrationThe reaction mixture was concentrated under reduced pressure and methanol
  5. additionwas added to the reaction
  6. customresulting in the formation of a white precipitate
  7. filtrationThe precipitate was collected by filtration
  8. customdried

Sources & evidence

ORD record
ord-7b5a98b2b24a481abfca0aff71a5de67
Source dataset
uspto-grants-2006_11
Patent number
US07141569B2

Reaction notes

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