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

HRID 630507Notes

Reaction equation

HRID 630507 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>[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

5

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 1

HCID 6228DimethylformamideSolvent2×

Procedure

(1H-Indol-6-yl)(morpholino)methanone (36.0 g, 156.5 mmol) in DMF (540 mL) was added drop wise at 0° C. to a solution of phosphoryl chloride (43.9 mL, 469 mmol) in DMF (884 mL) and the mixture was stirred at room temperature for 4 h. The reaction mixture was then neutralized with saturated sodium hydrogen carbonate solution and extracted with ethyl acetate (3×). The combined organic layers were dried over sodium sulfate and evaporated. The residue was finally purified by column chromatography [100-200 mesh silica; dichloromethane with 10% methanol]. White solid. Yield: 36 g (89% of theory)

Workup

  1. extractionextracted with ethyl acetate (3×)
  2. dry with materialThe combined organic layers were dried over sodium sulfate
  3. customevaporated
  4. customThe residue was finally purified by column chromatography [100-200 mesh silica; dichloromethane with 10% methanol]

Sources & evidence

ORD record
ord-1443a9e2e1064a49b7fb6530c3a07f0a
Source dataset
uspto-grants-2016_04
Patent number
US09315490B2

Reaction notes

Loading…