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

HRID 1112508Notes

Reaction equation

HRID 1112508 reaction equation
[CH3:1][C:2]1([CH2:7][CH2:8][CH2:9][NH:10][C:11]([C:13]2[NH:14][C:15]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)=[C:16]3[C:21]=2[CH:20]=[CH:19][C:18]([Cl:22])=[CH:17]3)=[O:12])[O:6][CH2:5][CH2:4][O:3]1.[Na].[CH3:30]OS(C1C=CC(C)=CC=1)(=O)=O>CN(C)C=O.CO>[CH3:1][C:2]1([CH2:7][CH2:8][CH2:9][NH:10][C:11]([C:13]2[N:14]([CH3:30])[C:15]([C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=3)=[C:16]3[C:21]=2[CH:20]=[CH:19][C:18]([Cl:22])=[CH:17]3)=[O:12])[O:3][CH2:4][CH2:5][O:6]1

Participants

6

Reactant 3

HCID 6645Methyl p-toluenesulfonateHCID 5360545SodiumHCID 543664105-Chloro-3-phenylisoindole-1-carboxylic acid [3-(2-methyl-1,3-dioxolan-2-yl)-propyl]amide

Product 1

HCID 538171005-Chloro-2-methyl-3-phenylisoindole-1-carboxylic acid [3-(2-methyl-1,3-dioxolan-2-yl)-propyl]amide

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent2×

Procedure

A solution of 24.0 g. of 5-chloro-3-phenylisoindole-1-carboxylic acid [3-(2-methyl-1,3-dioxolan-2-yl)-propyl]amide in 160 ml. of dimethylformamide is treated under an atmosphere of argon at 0°-5° C. with a solution of 2.1 g. of sodium in 40 ml. of methanol. The mixture is then stirred at room temperature for 30 minutes and subsequently added dropwise to a solution of 18.6 g. of p-toluenesulfonic acid methyl ester in 20 ml. of dimethylformamide. The mixture is subsequently stirred at room temperature for 30 minutes and then at 80° C. for 1 hour. After cooling, the mixture is poured on to 400 ml. of ice-water and, after the addition of 20 g. of sodium chloride, the separated product is removed by filtration under suction, washed with water and then dissolved in methylene chloride. The organic phase is washed with water, dried over sodium sulfate and evaporated to dryness. The residue obtained is chromatographed on 500 g. of silica gel using methylene chloride/ethyl acetate (4:1) for the elution. The uniform fractions are combined and evaporated, and there is obtained 5-chloro-2-methyl-3-phenylisoindole-1-carboxylic acid [3-(2-methyl-1,3-dioxolan-2-yl)-propyl]amide having a melting point of 137°-139° C. Recrystallization from ethanol yields colorless crystals of the same melting point.

Workup

  1. additionsubsequently added dropwise to a solution of 18.6 g
  2. stirringThe mixture is subsequently stirred at room temperature for 30 minutes
  3. waitat 80° C. for 1 hour
  4. temperatureAfter cooling
  5. additionthe mixture is poured on to 400 ml
  6. customof sodium chloride, the separated product is removed by filtration under suction
  7. washwashed with water
  8. dissolutiondissolved in methylene chloride
  9. washThe organic phase is washed with water
  10. dry with materialdried over sodium sulfate
  11. customevaporated to dryness
  12. customThe residue obtained
  13. customis chromatographed on 500 g
  14. washfor the elution
  15. customevaporated

Sources & evidence

ORD record
ord-e9ebaba8918b4d5b8331d39544a558a1
Source dataset
uspto-grants-1978_10
Patent number
US04122265

Reaction notes

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