Sodium Hydroxide → (S)-5-(2-Hydroxy-3-morpholin-4-yl-propyl)-3-methyl-4-oxo-1,4,5,6,7,8-hexahydro-pyrrolo[3,2-c]azepine-2-carbaldehyde

HRID 2191529Notes

Reaction equation

HRID 2191529 reaction equation
[Cl-].Cl[CH:3]=[N+](C)C.O[C@@H:8]([CH2:22][N:23]1[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1)[CH2:9][N:10]1[CH2:16][CH2:15][CH2:14][C:13]2[NH:17][CH:18]=[C:19]([CH3:20])[C:12]=2[C:11]1=[O:21].[OH-:29].[Na+].[Cl-].[Na+].[OH2:33]>ClCCl>[OH:29][C@@H:8]([CH2:22][N:23]1[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1)[CH2:9][N:10]1[CH2:16][CH2:15][CH2:14][C:13]2[NH:17][C:18]([CH:3]=[O:33])=[C:19]([CH3:20])[C:12]=2[C:11]1=[O:21]

Participants

6

Reactant 4

HCID 14798Sodium HydroxideHCID 77311Chloro-N,N-dimethylformiminium chlorideHCID 57417360Sodium chloride; waterHCID 59250058(S)-5-(2-hydroxy-3-morpholin-4-yl-propyl)-3-methyl-5,6,7,8-tetrahydro-1H-pyrrolo[3,2-c]azepin-4-one

Product 1

HCID 59250080(S)-5-(2-Hydroxy-3-morpholin-4-yl-propyl)-3-methyl-4-oxo-1,4,5,6,7,8-hexahydro-pyrrolo[3,2-c]azepine-2-carbaldehydeYield 61%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

(Chloromethylene)dimethylammonium chloride (130 mg, 0.977 mmol) was dissolved in 3 ml of dichloromethane under stirring under an argon atmosphere, the solution was cooled to 0° C. in ice-water bath. (S)-5-(2-hydroxy-3-morpholin-4-yl-propyl)-3-methyl-5,6,7,8-tetrahydro-1H-pyrrolo[3,2-c]azepin-4-one 78e (300 mg, 0.977 mmol) was dissolved in 2 ml of dichloromethane under stirring, the resulting solution was added to the above solution while maintaining the temperature below 0° C. Upon the completion of addition, the reaction mixture was stirred for 20 minutes at room temperature. After thin lay chromatography showed the disappearance of starting materials, the reaction solution was added with sodium hydroxide solution (12 mol/L) to quench the reaction. The reaction solution was added with 10 ml of saturated brine, extracted with the mixture solvent of dichloromethane and methanol (V:V=10:1) (100 ml×3), the combined organic phase was washed with saturated brine (100 ml×1), dried over anhydrous magnesium sulfate, filtered to remove the drying agent, the filtrate was concentrated under reduced pressure, the residue was purified by silica gel column chromatography to obtain the title compound (S)-5-(2-Hydroxy-3-morpholin-4-yl-propyl)-3-methyl-4-oxo-1,4,5,6,7,8-hexahydro-pyrrolo[3,2-c]azepine-2-carbaldehyde 78f (200 mg, yield 61%) as a white solid.

Workup

  1. stirringunder stirring
  2. additionthe resulting solution was added to the above solution
  3. temperaturewhile maintaining the temperature below 0° C
  4. additionUpon the completion of addition
  5. stirringthe reaction mixture was stirred for 20 minutes at room temperature
  6. customto quench
  7. customthe reaction
  8. extractionextracted with the mixture solvent of dichloromethane and methanol (V:V=10:1) (100 ml×3)
  9. washthe combined organic phase was washed with saturated brine (100 ml×1)
  10. dry with materialdried over anhydrous magnesium sulfate
  11. filtrationfiltered
  12. customto remove the drying agent
  13. concentrationthe filtrate was concentrated under reduced pressure
  14. customthe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-8c01ae8df857489294d026501050756c
Source dataset
uspto-grants-2012_12
Patent number
US08329682B2

Reaction notes

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