Dimethylformamide → HCID 2052444, compound

HRID 1166752Notes

Reaction equation

HRID 1166752 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[N:9]1[CH2:14][CH2:13][N:12]([CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:11][CH2:10]1.CN([CH:25]=[O:26])C.O=P(Cl)(Cl)Cl>>[CH3:1][C:2]1[CH:7]=[C:6]([CH:25]=[O:26])[C:5]([CH3:8])=[CH:4][C:3]=1[N:9]1[CH2:14][CH2:13][N:12]([CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:11][CH2:10]1

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 24813Phosphorus oxychlorideHCID 783543HCID 783543, compound

Product 1

HCID 2052444HCID 2052444, compoundYield 81.1%

Conditions

Temperature
0 °C

Procedure

The 4-(2,5-dimethylphenyl)-1-benzylpiperazine (10 g, 36 mmol) was dissolved in anhydrous DMF (30 mL, 390 mmol) and cooled to 0° C. Fresh POCl3 (70 mL, 750 mmol) was added drop wise with stirring. Once the addition was completed the dark mixture was warmed to 75° C. for five hours or until TLC analysis indicated the disappearance of the starting material. The excess phosphorous oxychloride was distilled off and the entire mixture was diluted with ethyl acetate and added slowly to 500 mL of ice-chips. The solution was neutralized and made basic with concentrated NaOH. The neutralization and basification must be done at low temperatures to avoid creating by-products. The formylated product was extracted with ethyl acetate (5×). The organic layer was washed with water (2×), brine, dried over magnesium sulfate and purified by silica gel column chromatography using gradient hexane/ethyl acetate (10/0 to 8/2). The product (9 g, 81%) was obtained as an oil.

Workup

  1. additionOnce the addition
  2. temperaturewas warmed to 75° C. for five hours or until TLC analysis
  3. distillationThe excess phosphorous oxychloride was distilled off
  4. additionthe entire mixture was diluted with ethyl acetate
  5. additionadded slowly to 500 mL of ice-chips
  6. extractionThe formylated product was extracted with ethyl acetate (5×)
  7. washThe organic layer was washed with water (2×), brine
  8. dry with materialdried over magnesium sulfate
  9. custompurified by silica gel column chromatography

Sources & evidence

ORD record
ord-aec4f4bf86de4aba8e35893368142d2d
Source dataset
uspto-grants-2003_09
Patent number
US06613942B1

Reaction notes

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