1,2-Dimethoxyethane → HCID 3345586, compound

HRID 849484Notes

Reaction equation

HRID 849484 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][N:3]=1.[Cl:9][CH2:10][C:11]([CH2:13]Cl)=O.COCCOC>C(O)C>[Cl:9][CH2:10][C:11]1[N:1]=[C:2]2[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][N:3]2[CH:13]=1

Participants

5

Reactant 3

HCID 80711,2-DimethoxyethaneHCID 107931,3-DichloroacetoneHCID 153482-Amino-5-methylpyridine

Product 1

HCID 3345586HCID 3345586, compoundYield 17.9%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of 2-amino-5-picoline (Aldrich; 5.028 g), 1,3-dichloroacetone (Aldrich; 5.893 g), and 1,2-dimethoxyethane (Aldrich; 43 mL) is stirred for 1 h at 55° C., at which time ethanol (47 mL) is added and the mixture is stirred for 2.75 h at reflux. The mixture is then concentrated under reduced pressure and partitioned between dichloromethane and saturated aq. sodium bicarbonate. The combined organic layers are washed with brine, dried with MgSO4, and concentrated under reduced pressure. The residue is chromatographed on silica gel using methanol/dichloromethane (1/99) and the appropriate fractions are combined and concentrated to give, after crystallization from ethyl acetate, 0.411 g of 2-(chloromethyl)-6-methylimidazo[1,2-a]pyridine. Methanol is added to the filtrate, which is then concentrated to a reduced volume. The addition of hexane gives an additional 1.50 g of 2-(chloromethyl)-6-methylimidazo[1,2-a]pyridine in two crops; mp 88-89.25° C.; ms m/z 180; IR (mineral oil) 796, 705, 699, 1343, 1510 cm-1 ; 1H NMR (CDCl3) δ 2.32, 4.76, 7.03, 7.47, 7.53, 7.86.

Workup

  1. additionis added
  2. temperatureat reflux
  3. concentrationThe mixture is then concentrated under reduced pressure
  4. custompartitioned between dichloromethane and saturated aq. sodium bicarbonate
  5. washThe combined organic layers are washed with brine
  6. dry with materialdried with MgSO4
  7. concentrationconcentrated under reduced pressure
  8. customThe residue is chromatographed on silica gel
  9. concentrationconcentrated
  10. customto give
  11. customafter crystallization from ethyl acetate, 0.411 g of 2-(chloromethyl)-6-methylimidazo[1,2-a]pyridine
  12. additionMethanol is added to the filtrate, which
  13. concentrationis then concentrated to a reduced volume
  14. additionThe addition of hexane

Sources & evidence

ORD record
ord-19a0ce69c72c49bd9a1cbbb77b2ce6c0
Source dataset
uspto-grants-2000_01
Patent number
US06013654

Reaction notes

Loading…