Dimethylformamide → HCID 13285855, compound

HRID 543718Notes

Reaction equation

HRID 543718 reaction equation
[H-].[Na+].[H][H].[CH:5]1[C:15]2[C:14](=[O:16])[NH:13][C:12]3[CH:17]=[CH:18][CH:19]=[CH:20][C:11]=3[NH:10][C:9]=2[CH:8]=[CH:7][CH:6]=1.[Na].O=P(Cl)(Cl)Cl.[OH-:27].[Na+].[CH3:29][N:30]([CH3:33])[CH:31]=O>>[CH3:29][N:30]1[CH2:33][CH2:5][C:15]([CH2:9][C:8]([N:10]2[C:9]3[CH:8]=[CH:7][CH:6]=[CH:5][C:15]=3[C:14](=[O:16])[NH:13][C:12]3[CH:17]=[CH:18][CH:19]=[CH:20][C:11]2=3)=[O:27])=[CH:14][CH2:31]1

Participants

8

Reactant 7

HCID 6228DimethylformamideHCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 24813Phosphorus oxychlorideHCID 2013275,10-Dihydro-11H-dibenzo(b,e)(1,4)diazepin-11-oneHCID 5360545SodiumHCID 178418361HCID 178418361, compound

Product 1

HCID 13285855HCID 13285855, compound

Conditions

Temperature
0 °C

Procedure

A mixture of 0.97 g (6.25 mol) of 1-methyl-1,2,5,6-tetrahydro-4-pyridinoacetic acid and 0.20 g (6.25 mmol) of 75% sodium hydride (in paraffin oil) in 16 ml of dimethylformamide was heated to 50°-80° C. until the development of hydrogen had ceased (2 to 3 hours). 1.312 g (6.24 mmol) of 5,10-dihydro-11H-dibenzo[b,e][1,4]diazepin-11-one was added to the sodium salt of the acid thus produced and at -10° C. 0.99 g of 98% phosphorus oxytrichloride was added dropwise within 10 minutes. The resulting mixture was stirred at -10° C. for 4 hours, at 0° C. for 4 hours and at ambient temperature for 20 hours. The mixture was stirred into 200 g of crushed ice, adjusted to pH 3.5 with sodium hydroxide solution, extracted once with methylene chloride and then the aqueous phase was adjusted to pH 9 and exhaustively extracted with methylene chloride. The organic phase was washed with water, dried over sodium sulphate and concentrated by evaporation in vacuo. After purification by column chromatography on silica gel (using ethyl acetate/methanol in a volume ratio of 9:1 as eluent) 0.63 g (29% of theory) of a colorless amorphous product was obtained, which was identical, according to the thin layer chromatogram, elementary analysis and IR spectrum, to a compound obtained using the method of Example 1.

Workup

  1. custom(2 to 3 hours)
  2. customthus produced and at -10° C
  3. extractionextracted once with methylene chloride
  4. extractionexhaustively extracted with methylene chloride
  5. washThe organic phase was washed with water
  6. dry with materialdried over sodium sulphate
  7. concentrationconcentrated by evaporation in vacuo
  8. customAfter purification by column chromatography on silica gel (
  9. customwas obtained
  10. customobtained

Sources & evidence

ORD record
ord-b523ee696e9e43b6a541db9763eb9700
Source dataset
uspto-grants-1984_05
Patent number
US04447434

Reaction notes

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