6-Chloro-2-picoline → 2-(6-Chloro-2-pyridinyl)-1-(3-methyl-2-furyl)ethanone

HRID 1269063Notes

Reaction equation

HRID 1269063 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([CH3:8])[CH:5]=[CH:4][CH:3]=1.[CH3:9][C:10]1[CH:14]=[CH:13][O:12][C:11]=1[C:15](OC)=[O:16].C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>O1CCCC1>[Cl:1][C:2]1[N:7]=[C:6]([CH2:8][C:15]([C:11]2[O:12][CH:13]=[CH:14][C:10]=2[CH3:9])=[O:16])[CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 876016-Chloro-2-picolineHCID 350231Methyl 3-methyl-2-furoateHCID 2733832Lithium Hexamethyldisilazide

Product 1

HCID 184466082-(6-Chloro-2-pyridinyl)-1-(3-methyl-2-furyl)ethanoneYield 94%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a cold (0° C.) solution of 6-chloro-2-picoline (25.8 mL 236 mmol) and methyl 3-methyl-2-furoate (33.08 g, 236 mmol) in tetrahydrofuran (300 mL) was added lithium bis(trimethylsilyl)amide (472 mL, 1.0 M in tetrahydrofuran, 472 mmol) dropwise via a pressure equalizing funnel over 1 hour. Upon complete addition, the cold bath was removed and the resultant solution was stirred at room temperature for 15 hours. The solution was concentrated. Methanol was added to quench the reaction resulting in a yellow solid precipitating. The precipitate was collected by filteration and washed with a small amount of cold methanol. 2-(6-Chloro-2-pyridinyl)-1-(3-methyl-2-furyl)ethanone (52.2 g, 94%) was obtained as a yellow solid. 1H NMR (CDCl3): δ 7.61 (t, 1H), 7.43 (s, 1H), 7.23 (m, 2H), 6.40 (s, 1H), 4.36 (s, 2H), 2.37 (s, 3H). MS m/z 236 (M+1).

Workup

  1. customover 1 hour
  2. additionUpon complete addition
  3. customthe cold bath was removed
  4. concentrationThe solution was concentrated
  5. additionMethanol was added
  6. customto quench the reaction
  7. customresulting in a yellow solid
  8. customprecipitating
  9. customThe precipitate was collected by filteration
  10. washwashed with a small amount of cold methanol

Sources & evidence

ORD record
ord-e3d6df7a2c8f44fdbde62e27b8170d48
Source dataset
uspto-grants-2007_04
Patent number
US07199120B2

Reaction notes

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