Phosphorus oxychloride → 6-(Morpholine-4-carbonyl)-1H-indole-3-carbaldehyde

HRID 630452Notes

Reaction equation

HRID 630452 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:10]([N:12]3[CH2:17][CH2:16][O:15][CH2:14][CH2:13]3)=[O:11])[CH:8]=2)[CH:3]=[CH:2]1.P(Cl)(Cl)(Cl)=O.[C:23](=O)([O-])[OH:24].[Na+]>CN(C=O)C.O>[N:12]1([C:10]([C:7]2[CH:8]=[C:9]3[C:4]([C:3]([CH:23]=[O:24])=[CH:2][NH:1]3)=[CH:5][CH:6]=2)=[O:11])[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1

Participants

6

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 516892Sodium BicarbonateHCID 39710543(1H-Indol-6-yl)(morpholino)methanone

Product 1

HCID 1186660826-(Morpholine-4-carbonyl)-1H-indole-3-carbaldehyde

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

A solution of (1H-indol-6-yl)(morpholino)methanone (200 mg, 0.869 mmol, 1.0 eq) in DMF (3.0 ml) was added dropwise at 0° C. to phosphorus oxychloride (0.34 mL, 2.60 mmol, 3.0 eq) in DMF (5.0 mL) under stirring. The mixture was stirred at room temperature for 3 h, then neutralized with saturated sodium hydrogen carbonate solution, diluted with water (20 mL), and extracted with ethyl acetate (2×10 mL). The organic layers were combined, washed with brine (20 mL), dried over sodium sulfate and evaporated. The residue was purified by silica gel column chromatography [100-200 mesh; methanol/dichloromethane=1:9]. White solid. Yield: 100 mg (45% of theory).

Workup

  1. stirringThe mixture was stirred at room temperature for 3 h
  2. extractionextracted with ethyl acetate (2×10 mL)
  3. washwashed with brine (20 mL)
  4. dry with materialdried over sodium sulfate
  5. customevaporated
  6. customThe residue was purified by silica gel column chromatography [100-200 mesh; methanol/dichloromethane=1:9]

Sources & evidence

ORD record
ord-984f016470c6402d825e249a38395338
Source dataset
uspto-grants-2016_04
Patent number
US09315490B2

Reaction notes

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