Sodium Hydroxide → HCID 23003163, compound

HRID 396205Notes

Reaction equation

HRID 396205 reaction equation
P(Cl)(Cl)(Cl)=O.[Cl:6][C:7]1[CH:28]=[CH:27][CH:26]=[C:25]([Cl:29])[C:8]=1[CH2:9][O:10][C:11]1[CH:12]=[C:13]2[C:17](=[CH:18][CH:19]=1)[N:16]([CH2:20][CH2:21][CH2:22][C:23]#[N:24])[CH:15]=[CH:14]2.ClC1C=CC=C(Cl)C=1[CH2:33][O:34]C1C=C2C(=CC=1)N(C(C)CC#N)C=C2.[OH-].[Na+]>CN(C=O)C>[Cl:6][C:7]1[CH:28]=[CH:27][CH:26]=[C:25]([Cl:29])[C:8]=1[CH2:9][O:10][C:11]1[CH:12]=[C:13]2[C:17](=[CH:18][CH:19]=1)[N:16]([CH2:20][CH2:21][CH2:22][C:23]#[N:24])[CH:15]=[C:14]2[CH:33]=[O:34]

Participants

6

Reactant 4

HCID 14798Sodium HydroxideHCID 24813Phosphorus oxychlorideHCID 23003160HCID 23003160, compoundHCID 23003165HCID 23003165, compound

Product 1

HCID 23003163HCID 23003163, compoundYield 70%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
0 °C

Procedure

A flame dried flask under argon was charged with DMF (0.43 mL, 5.57 mmol) and cooled to 0° C. Phosphorus oxychloride (0.16 mL, 1.67 mmol) was slowly added to the cooled DMF. The solution was stirred at 0° C. for 1 min and to this was added a DMF (1.5 mL) solution of a mixture of 4-[5-(2,6-dichlorobenzyloxy)indol-1-yl]butyronitrile (85%) and 3-[5-(2,6-dichlorobenzyloxy)indol-1-yl]butyronitrile (15%) (0.5 g, 1.4 mmol). The reaction mixture was stirred at room temprature for 1 h and heated at 50° C. for 4 h. The reaction solution was poured into ice water. A light yellow colored sticky solid precipated immediately. The mixture was neutralized by adding 1N NaOH until a pH of 7 was obtained. The product was extracted into ethyl acetate (3×) and the combined organic layers were washed with brine and dried over Na2SO4. The solvent was removed under reduced pressure and the resulting crude yellow oil was purified by flash column chromatography (silica gel, ethyl acetate/hexane) to yield the desired aldehyde as a white solid (0.38 g, 70%) and the undesired aldehyde (0.099 g, 18%).MS(ES) m/e 387.0 [M+H]+.

Workup

  1. customA flame dried flask under argon
  2. additionto this was added
  3. stirringThe reaction mixture was stirred at room temprature for 1 h
  4. temperatureheated at 50° C. for 4 h
  5. customwas obtained
  6. extractionThe product was extracted into ethyl acetate (3×)
  7. washthe combined organic layers were washed with brine
  8. dry with materialdried over Na2SO4
  9. customThe solvent was removed under reduced pressure
  10. customthe resulting crude yellow oil was purified by flash column chromatography (silica gel, ethyl acetate/hexane)

Sources & evidence

ORD record
ord-b7535f7772a4438b9f59e0cb62ed4268
Source dataset
uspto-grants-2003_08
Patent number
US06608059B1

Reaction notes

Loading…