Morpholine → HCID 178428040, compound

HRID 1764101Notes

Reaction equation

HRID 1764101 reaction equation
Cl.[NH2:2][C:3]1[CH:8]=[C:7](Cl)[CH:6]=[C:5]([CH3:10])[N+:4]=1[O-:11].[NH:12]1[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1>O>[NH2:2][C:3]1[CH:8]=[C:7]([N:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)[CH:6]=[C:5]([CH3:10])[N+:4]=1[O-:11]

Participants

4

Reactant 2

HCID 8083MorpholineHCID 178426121HCID 178426121, compound

Product 1

HCID 178428040HCID 178428040, compoundYield 27%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
180 °C

Procedure

A quantity (4.88 g., 0.025 mole) of 2-amino-4-chloro-6-methylpyridine-1-oxide hydrochloride (prepared in Part B, Example 1, above) with 20.0 ml. morpholine, and 20.0 ml. water was sealed in a reinforced bottle and heated in an oil bath at the temperature 180° C. for 6 hrs. The aqueous reaction mixture was cooled to 25° C. and then reheated to effect removal of excess morpholine and about one-half the water was removed by evaporation. This concentrate was then diluted with 50 ml. water and extracted with three 50-ml. portions of chloroform. The chloroform extracts were combined, dried over anhydrous sodium sulfate, treated with charcoal, and filtered. The chloroform was removed from the filtrate by evaporation under reduced pressure and the solid residue was triturated with acetone. The insolubles were collected on a filter. Testing via thin layer chromatography showed that there were three components. The components were separated by chromatography on a column of silica gel using a solvent mixture consisting of 1 part methanol and 9 parts methylene chloride. The fractions having the most rapidly moving component were collected and combined. The solvents were removed by evaporation. Chloroformic extraction of the original water-diluted reaction mixture was repeated followed by drying, treating with charcoal, filtration, and removal of chloroform was effected as before. This residue was combined with the residue from the chromatographic separation, and a crystallization and recrystallization from acetonitrile was effected. There was thus obtained 1.40 g. (27% yield) of 2-amino-6-methyl-4-morpholinopyridine-1-oxide as colorless needles having a melting point at 292° C. (with decomposition).

Workup

  1. temperatureThe aqueous reaction mixture was cooled to 25° C.
  2. customremoval of excess morpholine
  3. customabout one-half the water was removed by evaporation
  4. additionThis concentrate was then diluted with 50 ml
  5. extractionwater and extracted with three 50-ml
  6. dry with materialdried over anhydrous sodium sulfate
  7. additiontreated with charcoal
  8. filtrationfiltered
  9. customThe chloroform was removed from the filtrate by evaporation under reduced pressure
  10. customthe solid residue was triturated with acetone
  11. customThe insolubles were collected on a filter
  12. customThe components were separated by chromatography on a column of silica gel using a solvent mixture
  13. customwere collected
  14. customThe solvents were removed by evaporation
  15. extractionChloroformic extraction of the original water-
  16. additiondiluted
  17. customreaction mixture
  18. customby drying
  19. additiontreating with charcoal, filtration, and removal of chloroform
  20. customThis residue was combined with the residue from the chromatographic separation
  21. customa crystallization and recrystallization from acetonitrile

Sources & evidence

ORD record
ord-5e39c9ed5ba84837b3965c7f082fb330
Source dataset
uspto-grants-1978_09
Patent number
US04115396

Reaction notes

Loading…