Morpholine → HCID 23149914, compound

HRID 1670749Notes

Reaction equation

HRID 1670749 reaction equation
Cl.Cl[CH2:3][C:4]1[C:16]2[NH:15][C:14]3[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=3)[C:8]=2[CH2:7][CH2:6][N:5]=1.[NH:17]1[CH2:22][CH2:21][O:20][CH2:19][CH2:18]1.[BH4-].[Na+].[OH-].[Na+]>CO>[N:17]1([CH2:3][CH:4]2[C:16]3[NH:15][C:14]4[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=4)[C:8]=3[CH2:7][CH2:6][NH:5]2)[CH2:22][CH2:21][O:20][CH2:19][CH2:18]1

Participants

6

Reactant 4

HCID 8083MorpholineHCID 14798Sodium HydroxideHCID 4311764Sodium borohydrideHCID 135599827HCID 135599827, compound

Product 1

HCID 23149914HCID 23149914, compoundYield 83%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Under ice-cooling, 1-chloromethyl-4,9-dihydro-3H-β-carboline hydrochloride (synthesized according to the method described in J. Med. Chem., 34, 8, 1991, 2624-2633, 400 mg) was added to a mixture of morpholine (684 mg) and methanol (4.5 ml), and the mixture was stirred at room temperature for 6 hr. Under ice-cooling, sodium borohydride (119 mg) was added, and the mixture was stirred at room temperature for 16.5 hr. The reaction mixture was alkalified with a 1N aqueous sodium hydroxide solution, and the mixture was extracted with chloroform. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure to give a brown oil. The oil was purified by silica gel column chromatography (elution solvent: chloroform-methanol (20:1)) to give 1-(morpholine-4-ylmethyl)-2,3,4,9-tetrahydro-1H-β-carboline (353 mg, yield 83%).

Workup

  1. temperatureUnder ice-cooling
  2. temperatureUnder ice-cooling
  3. stirringthe mixture was stirred at room temperature for 16.5 hr
  4. extractionthe mixture was extracted with chloroform
  5. washThe organic layer was washed with saturated brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. customThe solvent was evaporated under reduced pressure
  8. customto give a brown oil
  9. customThe oil was purified by silica gel column chromatography (elution solvent: chloroform-methanol (20:1))

Sources & evidence

ORD record
ord-5584666457e3416d965fd9f6853cce67
Source dataset
uspto-grants-2011_08
Patent number
US07994196B2

Reaction notes

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