Sodium hydride → trans-Ethyl 2-(pyridin-4-YL)cyclopropanecarboxylate

HRID 1409126Notes

Reaction equation

HRID 1409126 reaction equation
[I-].[CH3:2][S+](C)C.[H-].[Na+].[CH2:8]([O:10][C:11](=[O:20])[CH:12]=[CH:13][C:14]1[CH:19]=[CH:18][N:17]=[CH:16][CH:15]=1)[CH3:9]>CS(C)=O>[N:17]1[CH:18]=[CH:19][C:14]([C@@H:13]2[CH2:2][C@H:12]2[C:11]([O:10][CH2:8][CH3:9])=[O:20])=[CH:15][CH:16]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 75127Trimethylsulfonium iodideHCID 53396309Ethyl 3-(pyridin-4-yl)acrylate

Product 1

HCID 59463128trans-Ethyl 2-(pyridin-4-YL)cyclopropanecarboxylateYield 18.7%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent2×

Procedure

Trimethylsulfonium iodide (1.50 g, 7.34 mmol) and sodium hydride (0.293 g, 7.34 mmol) were placed into a dry round bottom under nitrogen. DMSO (25 mL) was added and the mixture was stirred for 40 min. The solution turned cloudy. 3-Pyridin-4-yl-acrylic acid ethyl ester (7A, 1.0 g, 5.6 mmol) in DMSO (40 ml) was added dropwise at room temperature. The mixture was left to stir overnight and product was observed the next day by analytical HPLC. The reaction was quenched with 10 mL of water and the mixture was partitioned between ethyl acetate and water. The separated organic layer was dried over Mg2SO4, filtered, and concentrated under reduced pressure. The crude mixture was chromatographed on silica using 10-20% methanol/CH2Cl2 gradient, to give trans-ethyl 2-(pyridin-4-yl)cyclopropanecarboxylate (7B, 0.20 g, 18%) as a cream solid. 1H NMR (METHANOL-d4) δ: 8.39 (d, J=6.1 Hz, 2H), 7.21 (d, J=6.1 Hz, 2H), 4.17 (q, J=7.1 Hz, 2H), 2.42-2.55 (m, 1H), 2.02-2.13 (m, 1H), 1.59-1.69 (m, 1H), 1.42-1.51 (m, 1H), 1.27 (t, 3H). ESI-MS: m/z 192.0 (M+H)+.

Workup

  1. waitThe mixture was left
  2. stirringto stir overnight
  3. customThe reaction was quenched with 10 mL of water
  4. customthe mixture was partitioned between ethyl acetate and water
  5. dry with materialThe separated organic layer was dried over Mg2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude mixture was chromatographed on silica using 10-20% methanol/CH2Cl2 gradient

Sources & evidence

ORD record
ord-d80d83c05a7a40ca8c0a9137fd56e43e
Source dataset
uspto-grants-2014_12
Patent number
US08921358B2

Reaction notes

Loading…