Dimethylformamide → 5-Chloro-3-phenylisoindole-1-carboxylic acid [3-(2-methyl-1,3-dioxolan-2-yl)-propyl]amide

HRID 1863090Notes

Reaction equation

HRID 1863090 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]([CH2:12][CH2:13][CH2:14][C:15]3([CH3:20])[O:19][CH2:18][CH2:17][O:16]3)[C:10](=[O:21])[CH2:9][N:8]=[C:7]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[C:6]=2[CH:28]=1.CN(C)C=O.[H-].[Na+]>O>[CH3:20][C:15]1([CH2:14][CH2:13][CH2:12][NH:11][C:10]([C:9]2[NH:8][C:7]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[C:6]3[C:5]=2[CH:4]=[CH:3][C:2]([Cl:1])=[CH:28]3)=[O:21])[O:19][CH2:18][CH2:17][O:16]1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 203933607-chloro-1,3-dihydro-1-[3-(2-methyl-1,3-dioxolan-2-yl)propyl]-5-phenyl-2H-1,4-benzodiazepin-2-one

Product 1

HCID 543664105-Chloro-3-phenylisoindole-1-carboxylic acid [3-(2-methyl-1,3-dioxolan-2-yl)-propyl]amide

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
60 °C

Procedure

A solution of 40.0 g. of 7-chloro-1,3-dihydro-1-[3-(2-methyl-1,3-dioxolan-2-yl)-propyl]-5-phenyl-2H-1,4-benzodiazepin-2-one in 500 ml. of dimethylformamide is treated under an atmosphere of argon at room temperature with 0.115 mol. of sodium hydride (5.1 g. of a 55% dispersion in mineral oil). The mixture is warmed to 60° C. over a period of about 30 minutes, then stirred at this temperature for 1 hour and thereafter at 70° C. for an additional hour. After cooling, 10 ml. of water are added dropwise and the mixture is poured on to 4 liters of ice-water. After the addition of 150 g. of sodium chloride, the separated product is removed by filtration, washed with water and dissolved in methylene chloride. The organic solution is dried over sodium sulfate and concentrated to dryness. The residue is chromatographed on 1000 g. of silica gel using methylene chloride/ethyl acetate (4:1) for the elution. The homogeneous fractions are combined and evaporated. The residual oil crystallizes upon trituration with hexane, and there is obtained 5-chloro-3-phenylisoindole-1-carboxylic acid [3-(2-methyl-1,3-dioxolan-2-yl)propyl]amide in the form of yellowish crystals having a melting point of 157°-159° C. Recrystallization from ethanol does not increase the melting point.

Workup

  1. waitat 70° C. for an additional hour
  2. temperatureAfter cooling
  3. additionAfter the addition of 150 g
  4. customof sodium chloride, the separated product is removed by filtration
  5. washwashed with water
  6. dissolutiondissolved in methylene chloride
  7. dry with materialThe organic solution is dried over sodium sulfate
  8. concentrationconcentrated to dryness
  9. customThe residue is chromatographed on 1000 g
  10. washfor the elution
  11. customevaporated
  12. customThe residual oil crystallizes upon trituration with hexane

Sources & evidence

ORD record
ord-6a9063c3fbaf4fcf96d3edebdd84d612
Source dataset
uspto-grants-1979_09
Patent number
US04167632

Reaction notes

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