Hexamethylphosphoramide → 5-Chloro-2-[(diethylcarbamoyl)methyl]-3-phenylisoindole-1-carboxylic acid ethyl ester

HRID 1679063Notes

Reaction equation

HRID 1679063 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].CN(C)P(=O)(N(C)C)N(C)C.[H-].[Na+].[CH2:35]([N:37]([CH2:42][CH3:43])[C:38](=[O:41])[CH2:39]Cl)[CH3:36]>C(O)C>[CH2:1]([O:3][C:4]([C:6]1[N:7]([CH2:39][C:38](=[O:41])[N:37]([CH2:42][CH3:43])[CH2:35][CH3:36])[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 12679HexamethylphosphoramideHCID 16844Chloro-N,N-diethylacetamideHCID 24758Sodium hydrideHCID 54174784Ethyl 5-chloro-3-phenyl-2H-isoindole-1-carboxylate

Product 1

HCID 544691795-Chloro-2-[(diethylcarbamoyl)methyl]-3-phenylisoindole-1-carboxylic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 15.0 g. of 5-chloro-3-phenylisoindole-1-carboxylic acid ethyl ester in 250 ml. of hexamethylphosphoric acid triamide is treated under nitrogen at 5° C. with 0.055 mol. of sodium hydride (2.5 g. of a 55% dispersion in mineral oil) and then stirred at the same temperature for 15 minutes. At 5°-10° C. a solution of 15 g. of N,N-diethylchloroacetamide in 40 ml. of ethanol is added thereto and the mixture stirred for 30 minutes at room temperature and subsequently heated for 4 hours at 80° C. The mixture is cooled and poured into 2.5 liters of ice-water. After the addition of 150 g. of sodium chloride, the separated product is removed by filtration under suction, washed with water and then dissolved in methylene chloride. The aqueous layer is separated, the organic phase dried over sodium sulfate, filtered and evaporated to dryness. The residue is triturated with 100 ml. of ether, the unreacted starting material crystallizes out. The latter is removed by filtration under vacuum and washed with ether. The ethereal filtrate is evaporated to dryness. The oily residue is cooled and triturated with ether, crystals being obtained. Recrystallization from ethanol yields 5-chloro-2-[(diethylcarbamoyl)methyl]-3-phenylisoindole-1-carboxylic acid ethyl ester; melting point 118°-120° C.

Workup

  1. customAt 5°-10° C.
  2. stirringthe mixture stirred for 30 minutes at room temperature
  3. temperatureThe mixture is cooled
  4. additionAfter the addition of 150 g
  5. customof sodium chloride, the separated product is removed by filtration under suction
  6. washwashed with water
  7. dissolutiondissolved in methylene chloride
  8. customThe aqueous layer is separated
  9. dry with materialthe organic phase dried over sodium sulfate
  10. filtrationfiltered
  11. customevaporated to dryness
  12. customThe residue is triturated with 100 ml
  13. customcrystallizes out
  14. customThe latter is removed by filtration under vacuum
  15. washwashed with ether
  16. customThe ethereal filtrate is evaporated to dryness
  17. temperatureThe oily residue is cooled
  18. customtriturated with ether, crystals
  19. custombeing obtained
  20. customRecrystallization from ethanol

Sources & evidence

ORD record
ord-028b5545d56a413ca6f3697ea2a1d80e
Source dataset
uspto-grants-1978_03
Patent number
US04077978

Reaction notes

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