Morpholine → HCID 20081794, compound

HRID 1609565Notes

Reaction equation

HRID 1609565 reaction equation
[CH:1]([C:4]1[NH:5][C:6]([CH:25]([CH3:27])[CH3:26])=[C:7]([C:22]([O-:24])=O)[CH:8]([C:15]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=2)[C:9]=1[C:10]([O:12][CH2:13][CH3:14])=[O:11])([CH3:3])[CH3:2].[NH:28]1[CH2:33][CH2:32][O:31][CH2:30][CH2:29]1>O1CCCC1>[CH:1]([C:4]1[NH:5][C:6]([CH:25]([CH3:27])[CH3:26])=[C:7]([C:22]([N:28]2[CH2:33][CH2:32][O:31][CH2:30][CH2:29]2)=[O:24])[CH:8]([C:15]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=2)[C:9]=1[C:10]([O:12][CH2:13][CH3:14])=[O:11])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 8083MorpholineHCID 20081843HCID 20081843, compound

Product 1

HCID 20081794HCID 20081794, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

1.05 g (6.5 mmol) of N,N'-carbonylimidazole are added under a nitrogen atmosphere to 1.875 g (5 mmol) of the compound from Example 95 dissolved in 20 ml of dry tetrahydrofuran and the mixture is stirred for 30 minutes at room temperature. It is subsequently heated to reflux for 30 minutes, a solution of 0.87 ml (10 mmol) of morpholine in 5 ml of dry tetrahydrofuran is added and it is heated to boiling for a further 2 hours. After cooling to room temperature, the mixture is concentrated in vacuo and the residue is taken up in dichloromethane and washed successively with 1N hydrochloric acid, 1N sodium hydroxide solution and water. The organic phase is dried over magnesium sulphate and concentrated in vacuo, and the crystalline residue is dried in a desiccator.

Workup

  1. temperatureIt is subsequently heated
  2. temperatureto reflux for 30 minutes
  3. temperatureit is heated
  4. waitto boiling for a further 2 hours
  5. temperatureAfter cooling to room temperature
  6. concentrationthe mixture is concentrated in vacuo
  7. washwashed successively with 1N hydrochloric acid, 1N sodium hydroxide solution and water
  8. dry with materialThe organic phase is dried over magnesium sulphate
  9. concentrationconcentrated in vacuo
  10. customthe crystalline residue is dried in a desiccator

Sources & evidence

ORD record
ord-e395eb3fdc2440ffa22d3ee115c1db83
Source dataset
uspto-grants-1995_03
Patent number
US05401746

Reaction notes

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