Triethylamine → 5-Chloro-3-[2-(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)-2-oxoethyl]-2-(4-methoxyphenyl)-2,3-dihydro-1H-isoindol-1-one

HRID 868251Notes

Reaction equation

HRID 868251 reaction equation
[O:1]1[C:5]2([CH2:10][CH2:9][NH:8][CH2:7][CH2:6]2)[O:4][CH2:3][CH2:2]1.C(N(CC)CC)C.P(C#N)(=O)(OCC)OCC.[Cl:28][C:29]1[CH:37]=[C:36]2[C:32]([C:33](=[O:50])[N:34]([C:42]3[CH:47]=[CH:46][C:45]([O:48][CH3:49])=[CH:44][CH:43]=3)[CH:35]2[CH2:38][C:39](O)=[O:40])=[CH:31][CH:30]=1>CN(C)C=O>[Cl:28][C:29]1[CH:37]=[C:36]2[C:32](=[CH:31][CH:30]=1)[C:33](=[O:50])[N:34]([C:42]1[CH:47]=[CH:46][C:45]([O:48][CH3:49])=[CH:44][CH:43]=1)[CH:35]2[CH2:38][C:39]([N:8]1[CH2:9][CH2:10][C:5]2([O:4][CH2:3][CH2:2][O:1]2)[CH2:6][CH2:7]1)=[O:40]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 674351,4-Dioxa-8-azaspiro(4.5)decaneHCID 76257Diethyl cyanophosphonateHCID 13935113HCID 13935113, compound

Product 1

HCID 136559255-Chloro-3-[2-(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)-2-oxoethyl]-2-(4-methoxyphenyl)-2,3-dihydro-1H-isoindol-1-oneYield 90.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

With ice-cooling and stirring, 1.57 g of 1,4-dioxa-8-azaspiro[4.5]decane, 2.3 ml of triethylamine and 2.12 g of diethyl phosphorocyanidate were successively added to a solution of 3.32 g of 6-chloro-2-(4-methoxyphenyl)-3-oxoisoindoline-1-acetic acid in 30 ml of dimethylformamide. The mixture was stirred with ice-cooling for an hour. To the reaction mixture was added 150 ml of ice water and the mixture was allowed to stand to give a crystalline precipitate, which was collected by filtration, washed with water and dried. Recrystallization from ether gave 4.13 g of colorless crystals melting at 156°-157° C.

Workup

  1. temperatureWith ice-cooling
  2. stirringThe mixture was stirred with ice-
  3. temperaturecooling for an hour
  4. customto give a crystalline precipitate, which
  5. filtrationwas collected by filtration
  6. washwashed with water
  7. customdried
  8. customRecrystallization from ether

Sources & evidence

ORD record
ord-46caabc0b8f946d9bec390bb54a917af
Source dataset
uspto-grants-1988_10
Patent number
US04778801

Reaction notes

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