Ethyl Acetate → Methyl 2-(5-bromopyridin-3-yl)cyclopropanecarboxylate

HRID 391347Notes

Reaction equation

HRID 391347 reaction equation
[H-].[Na+].[I-].C[S+](C)(C)=O.[Br:9][C:10]1[CH:11]=[C:12](/[CH:16]=[CH:17]/[C:18]([O:20][CH3:21])=[O:19])[CH:13]=[N:14][CH:15]=1.[CH3:22]COC(C)=O>CS(C)=O>[Br:9][C:10]1[CH:11]=[C:12]([CH:16]2[CH2:22][CH:17]2[C:18]([O:20][CH3:21])=[O:19])[CH:13]=[N:14][CH:15]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 74498Sulfoxonium, trimethyl-, iodide (1:1)HCID 59578421methyl (2E)-3-(5-bromopyridin-3-yl)prop-2-enoate

Product 1

HCID 59578427Methyl 2-(5-bromopyridin-3-yl)cyclopropanecarboxylateYield 24%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent2×

Procedure

DMSO (20 ml) was added slowly to a mixture of sodium hydride (0.215 g, 5.37 mmol) and trimethylsulfoxonium iodide (1.227 g, 5.58 mmol). The mixture was stirred at room temperature for 15 min, and then (E)-methyl 3-(5-bromopyridin-3-yl)acrylate (1 g, 4.13 mmol) in DMSO (8 ml) was added. The reaction mixture was stirred at room temperature for 3 min. Ice water and EtOAc were added. The organic layer was washed with water and brine. The aqueous layer was extracted with EtOAc twice. The combined organic layer was dried over Na2SO4, filtered and concentrated. The residue was purified via flash column (EtOAc/Heptane=0-30%, v/v) to give methyl 2-(5-bromopyridin-3-yl)cyclopropanecarboxylate (257 mg, 1.004 mmol, 24% yield). ESI-MS m/z: 358[M+1]+; 1H NMR (CDCl3, 400 MHz); 1.33-1.38 (m, 1H), 1.66-1.71 (m, 1H), 1.94-1.98 (m, 1H), 2.49-2.54 (m, 1H), 3.75 (s, 3H), 7.51 (t, J=2.0 Hz, 1H), 8.37 (d, J=2.0 Hz, 1H), 8.53 (t, J=2.0 Hz, 1H).

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 3 min
  2. washThe organic layer was washed with water and brine
  3. extractionThe aqueous layer was extracted with EtOAc twice
  4. dry with materialThe combined organic layer was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified via flash column (EtOAc/Heptane=0-30%, v/v)

Sources & evidence

ORD record
ord-fff9d48e97cb43cd8cec3a032d209fa1
Source dataset
uspto-grants-2013_02
Patent number
US08383827B2

Reaction notes

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