Sodium Chloride → 2-(4-Bromobutyl)-5-chloro-3-phenylisoindole-1-carboxylic acid ethyl ester

HRID 372308Notes

Reaction equation

HRID 372308 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[NH:7][C:8]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[C:9]2[C:14]=1[CH:13]=[CH:12][C:11]([Cl:15])=[CH:10]2)=[O:5])[CH3:2].[H-].[Na+].[Br:24][CH2:25][CH2:26][CH2:27][CH2:28]Br.[Cl-].[Na+]>CN(C)C=O>[CH2:1]([O:3][C:4]([C:6]1[N:7]([CH2:28][CH2:27][CH2:26][CH2:25][Br:24])[C:8]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[C:9]2[C:14]=1[CH:13]=[CH:12][C:11]([Cl:15])=[CH:10]2)=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 5234Sodium ChlorideHCID 80561,4-DibromobutaneHCID 24758Sodium hydrideHCID 54174784Ethyl 5-chloro-3-phenyl-2H-isoindole-1-carboxylate

Product 1

HCID 542186872-(4-Bromobutyl)-5-chloro-3-phenylisoindole-1-carboxylic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

A solution of 12.0 g. of 5-chloro-3-phenylisoindole-1-carboxylic acid ethyl ester in 240 ml. of dimethylformamide is treated under nitrogen at -10° C. with 0.08 mol. of sodium hydride (3.5 g. of a 55% dispersion in mineral oil) and stirred in an ice-bath for 30 minutes. Then, there are added thereto at -10° C. 26.0 g. of 1,4-dibromobutane in one batch; the mixture is thereafter stirred at room temperature for 1 hour and subsequently heated at 60° C. for 18 hours. After cooling, the mixture is poured into 2 liters of ice-water, 100 g. of sodium chloride are added and the separated oily product is immediately extracted with methylene chloride. The organic phase, shielded from daylight, is washed with a solution of sodium chloride, dried over sodium sulfate and evaporated to dryness under reduced pressure. The resulting oil is taken up in chloroform and chromatographed on 500 g. of silica gel with chloroform/n-heptane/ethanol (10:10:1) as the eluant, care is taken that the eluate remains shielded from daylight. The uniform fractions are combined and evaporated, and there is obtained 2-(4-bromobutyl)-5-chloro-3-phenylisoindole-1-carboxylic acid ethyl ester as an oil, which has to be employed in the next stage as quickly as possible.

Workup

  1. additionThen, there are added
  2. customat -10° C
  3. stirringthe mixture is thereafter stirred at room temperature for 1 hour
  4. temperatureAfter cooling
  5. extractionthe separated oily product is immediately extracted with methylene chloride
  6. washis washed with a solution of sodium chloride
  7. dry with materialdried over sodium sulfate
  8. customevaporated to dryness under reduced pressure
  9. customchromatographed on 500 g
  10. customevaporated

Sources & evidence

ORD record
ord-ef80d0493bbd4355b39c9eb12b2abc10
Source dataset
uspto-grants-1978_05
Patent number
US04090027

Reaction notes

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