Morpholine → HCID 70564713, compound

HRID 1659860Notes

Reaction equation

HRID 1659860 reaction equation
[CH3:1][C:2]1([CH3:31])[C:25]2[CH2:24][CH2:23][N:22](C(=O)CCO)[CH2:21][C:20]=2[C:5]2[C:6]([OH:19])=[CH:7][C:8]([CH:10]([CH3:18])[CH:11]([CH3:17])[CH2:12][CH2:13][CH2:14][CH2:15][CH3:16])=[CH:9][C:4]=2[O:3]1.Br[CH2:33][C:34](Br)=[O:35].C(N(CC)CC)C.[NH:44]1[CH2:49][CH2:48][O:47][CH2:46][CH2:45]1>C(Cl)Cl.O>[CH3:31][C:2]1([CH3:1])[CH:25]2[C:20](=[C:21]([C:34](=[O:35])[CH2:33][N:44]3[CH2:49][CH2:48][O:47][CH2:46][CH2:45]3)[NH:22][CH2:23][CH2:24]2)[C:5]2[C:6]([OH:19])=[CH:7][C:8]([CH:10]([CH3:18])[CH:11]([CH3:17])[CH2:12][CH2:13][CH2:14][CH2:15][CH3:16])=[CH:9][C:4]=2[O:3]1

Participants

7

Reactant 4

HCID 8083MorpholineHCID 8471TriethylamineHCID 61147Bromoacetyl bromideHCID 12800744HCID 12800744, compound

Product 1

HCID 70564713HCID 70564713, compoundYield 28.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent4×

Procedure

To an ice cold, stirred solution of 7.16 g (0.02 mole) of compound 1 (Scheme 3) in 40 ml of methylene chloride were added dropwise 9.70 g (0.048 mole) of bromoacetyl bromide dissolved in 10 ml of methylene chloride followed by a solution of 4.84 g (0.048 mole) of triethylamine in 10 ml of methylene chloride. The temperature was maintained below 8° C. during both additions. The reaction mixture was stirred in an ice bath for 1.5 hours and then at room temperature for 4 hours. Most of the solvent was removed under a rapid stream of nitrogen in a water bath held at 35°-40° C. The residue was taken up in 40 ml of dry dimethylformamide cooled in ice and treated dropwise with 8.71 g (0.10 mole) of morpholine, keeping the reaction temperature below 15° C. After being stirred at room temperature overnight, the reaction mixture was poured into water, insoluble material was taken up in methylene chloride, washed with water and concentrated to dryness. The residue (11.3 g) was taken up in 100 ml of methanol, cooled in ice, treated with 10 ml of 45 percent potassium hydroxide solution and stirred at room temperature under a nitrogen atmosphere for 2 hours. The solution was cooled in ice and neutralized to pH 9 (approximate) using 6 N hydrochloric acid and dry ice. The precipitate (about 11 g) was collected at the filter and shaken with a mixture of water and methylene chloride until solution was complete. The organic layer was separated, washed with water and concentrated to dryness. The crystalline residue (5.0 g), m.p. 205°-215° C., was recrystallized from dimethoxyethane to give 2.76 g of the above-titled compound, m.p. 217°-219° C.

Workup

  1. temperatureThe temperature was maintained below 8° C. during both additions
  2. waitat room temperature for 4 hours
  3. customMost of the solvent was removed under a rapid stream of nitrogen in a water bath
  4. customheld at 35°-40° C
  5. temperaturecooled in ice
  6. customthe reaction temperature below 15° C
  7. stirringAfter being stirred at room temperature overnight
  8. washwashed with water
  9. concentrationconcentrated to dryness
  10. temperaturecooled in ice
  11. additiontreated with 10 ml of 45 percent potassium hydroxide solution
  12. stirringstirred at room temperature under a nitrogen atmosphere for 2 hours
  13. temperatureThe solution was cooled in ice and neutralized to pH 9 (approximate)
  14. customThe precipitate (about 11 g) was collected at the
  15. filtrationfilter
  16. stirringshaken with a mixture of water and methylene chloride until solution
  17. customThe organic layer was separated
  18. washwashed with water
  19. concentrationconcentrated to dryness
  20. customThe crystalline residue (5.0 g), m.p. 205°-215° C., was recrystallized from dimethoxyethane

Sources & evidence

ORD record
ord-bd2507b5405243cea121e6aca9d3f634
Source dataset
uspto-grants-1981_12
Patent number
US04305938

Reaction notes

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