Pyridine → 4-(Chloromethyl)-1,4-dimethylimidazolidin-2-one

HRID 1025924Notes

Reaction equation

HRID 1025924 reaction equation
O[CH2:2][C:3]1([CH3:10])[CH2:7][N:6]([CH3:8])[C:5](=[O:9])[NH:4]1.N1C=CC=CC=1.S(Cl)([Cl:19])=O>ClCCCl>[Cl:19][CH2:2][C:3]1([CH3:10])[CH2:7][N:6]([CH3:8])[C:5](=[O:9])[NH:4]1

Participants

5

Reactant 3

HCID 1049PyridineHCID 24386Thionyl ChlorideHCID 675087194-(Hydroxymethyl)-1,4-dimethylimidazolidin-2-one

Product 1

HCID 867145864-(Chloromethyl)-1,4-dimethylimidazolidin-2-oneYield 25%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A solution of 4-(hydroxymethyl)-1,4-dimethylimidazolidin-2-one (3.3 g, 22.7 mmol), anhydrous pyridine (8.25 ml, 102 mmol), and thionyl chloride (8.26 ml, 114 mmol) in 46 ml of 1,2-dichloroethane was heated at reflux temperature for 8 hours. The reaction mixture was concentrated under reduced pressure, diluted with dichloromethane, and filtered to remove solids. The organic layer was washed with once 2 N HCl, which was back-extracted three times with dichloromethane, and the combined organic fractions were dried over sodium sulfate and concentrated to 2.2 g of yellow oil. The crude product was purified by column chromatorgraphy, eluting from silica gel with a gradient of 0-10% methanol in dichloromethane to give 897 mg of desired product as a white solid (25% yield). 1H NMR (400 MHz, CDCl3) δ 1.42 (s, 3H), 2.79 (s, 3H), 3.17-3.20 (d, J=9.2 Hz, 1H), 3.36-3.39 (d, J=9.2 Hz, 1H), 3.50 (s, 2H). 13C NMR (100 MHz, CDCl3) δ 24.2, 30.3, 51.5, 55.0, 57.0, 160.6. LRMS (ESI/APCI): 163 [M+H]+.

Workup

  1. temperatureat reflux temperature for 8 hours
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. additiondiluted with dichloromethane
  4. filtrationfiltered
  5. customto remove solids
  6. washThe organic layer was washed with once 2 N HCl, which
  7. extractionwas back-extracted three times with dichloromethane
  8. dry with materialthe combined organic fractions were dried over sodium sulfate
  9. concentrationconcentrated to 2.2 g of yellow oil
  10. customThe crude product was purified by column chromatorgraphy
  11. washeluting from silica gel with a gradient of 0-10% methanol in dichloromethane

Sources & evidence

ORD record
ord-56c81499c2c84144828560bc888b1d94
Source dataset
uspto-grants-2014_05
Patent number
US08729112B2

Reaction notes

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