Morpholine → HCID 23144211, compound

HRID 337512Notes

Reaction equation

HRID 337512 reaction equation
[O:1]1[CH2:6][CH2:5][CH:4]([C:7]([C:9]2[S:13][C:12]([NH2:14])=[N:11][C:10]=2[C:15]2[O:16][CH:17]=[CH:18][CH:19]=2)=[O:8])[CH2:3][CH2:2]1.C(N(CC)CC)C.Br[CH2:28][C:29](Br)=[O:30].[NH:32]1[CH2:37][CH2:36][O:35][CH2:34][CH2:33]1>C1COCC1.C(OCC)(=O)C.O>[O:16]1[CH:17]=[CH:18][CH:19]=[C:15]1[C:10]1[N:11]=[C:12]([NH:14][C:29](=[O:30])[CH2:28][N:32]2[CH2:37][CH2:36][O:35][CH2:34][CH2:33]2)[S:13][C:9]=1[C:7]([CH:4]1[CH2:5][CH2:6][O:1][CH2:2][CH2:3]1)=[O:8]

Participants

8

Reactant 4

HCID 8083MorpholineHCID 8471Triethylamine2×HCID 61147Bromoacetyl bromide2×HCID 866124682-Amino-4-(2-furyl)-5-(tetrahydropyran-4-ylcarbonyl)thiazole

Product 1

HCID 23144211HCID 23144211, compoundYield 40.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent4×HCID 8857Ethyl AcetateSolvent

Procedure

Compound 454 (13.9 g, 50.0 mmol) and triethylamine (15.3 mL, 110 mmol) were suspended in THF (200 mL), and a solution (50 mL) of bromoacetyl bromide (8.80 mL, 100 mmol) in THF was added dropwise thereto at 0° C., followed by stirring at room temperature for 1 hour. At 0° C., a solution (100 mL) of bromoacetyl bromide (17.6 mL, 200 mmol) in THF was added to the reaction mixture, followed by stirring at room temperature for 2 hours. At 0° C., a solution (100 mL) of morpholine (61.2 mL, 700 mmol) and triethylamine (97.6 mL, 700 mmol) in THF was added dropwise to the reaction mixture, followed by stirring at room temperature for 30 minutes. The reaction mixture was poured into a mixture of water (500 mL) and ethyl acetate (500 mL), followed by filtration, and the resulting filtrate was subjected to liquid-liquid separation. The organic layer was washed successively with a saturated aqueous solution of sodium hydrogencarbonate and a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled away under reduced pressure. The resulting residue was purified through silica gel column chromatography (chloroform:methanol=97:3), followed by recrystallizing from ethanol to afford the entitled Compound 558 (8.17 g, 40%) as a pale brown solid.

Workup

  1. customat 0° C.
  2. stirringby stirring at room temperature for 2 hours
  3. stirringby stirring at room temperature for 30 minutes
  4. filtrationfollowed by filtration
  5. customthe resulting filtrate was subjected to liquid-liquid separation
  6. washThe organic layer was washed successively with a saturated aqueous solution of sodium hydrogencarbonate
  7. dry with materiala saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate
  8. distillationthe solvent was distilled away under reduced pressure
  9. customThe resulting residue was purified through silica gel column chromatography (chloroform:methanol=97:3)
  10. customby recrystallizing from ethanol

Sources & evidence

ORD record
ord-a6f1d11ba0d8411f91a5393a182c21b3
Source dataset
uspto-grants-2014_11
Patent number
US08889718B2

Reaction notes

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