Nitrogen → HCID 59594378, compound

HRID 1186059Notes

Reaction equation

HRID 1186059 reaction equation
N#N.[Cl:3][C:4]1[CH:15]=[C:8]2[C:9]([O:11][C:12](=[O:14])[NH:13][C:7]2=[CH:6][CH:5]=1)=[O:10].[CH3:16][O:17][C:18]1[CH:25]=[CH:24][C:21]([CH2:22]Cl)=[CH:20][CH:19]=1.[H-].[Na+]>C1COCC1.[I-].C([N+](CCCC)(CCCC)CCCC)CCC.[H-].[Na+]>[Cl:3][C:4]1[CH:5]=[CH:6][C:7]2[N:13]([CH2:22][C:21]3[CH:24]=[CH:25][C:18]([O:17][CH3:16])=[CH:19][CH:20]=3)[C:12](=[O:14])[O:11][C:9](=[O:10])[C:8]=2[CH:15]=1

Participants

8

Reactant 4

HCID 947NitrogenHCID 24758Sodium hydrideHCID 699934-Methyloxybenzyl chlorideHCID 784805-Chloroisatoic anhydride2×

Product 1

HCID 59594378HCID 59594378, compoundYield 193.7%

Reagents, catalysts & solvents 3

HCID 24758Sodium hydrideCatalystHCID 67553Tetrabutylammonium IodideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

In a 3 L, 3-neck RBF equipped with mechanical stir, thermocouple and N2 inlet, 90 g (0.455 mol) of 5-chloroisatoic anhydride was suspended in anhydrous THF (0.9 L). Under N2, 4-methoxybenzylchloride (75 g, 0.48 mol) was added followed by the addition of tetrabutylammonium iodide (84 g, 0.23 mol). The reaction mixture was stirred for 5 min at room temperature and then 20 g (0.5 mol) of NaH was added portion-wise over 20 min (reaction temperature increased to 29° C. due to an exotherm and therefore reaction mixture was placed into water bath to keep the temperature below 30° C.). Reaction was stirred for 16 h (RT). Next day HPLC showed about 26% unreacted 5-chloroisatoic anhydride. Additional NaH (1 g) was added and the reaction mixture was heated to 32° C. and stirred for another 5 h. NMR showed that all of the starting material had been consumed. Reaction was quenched by adding 10 g of glacial acetic acid slowly followed by stirring for 30 min. Reaction mixture was filtered through celite and filter cake was washed with THF. Filtrate was concentrated to give 280 g of crude product (yellow-brown solid), which was used with no further purification. 1H NMR (300 MHz, DMSO-d6) δ 3.8 (s, 3H), 5.25 (s, 2H), 6.8 (d, 2H), 7.2 (m, 3H), 7.75 (d, 1 H), 7.9 (d, 1H).

Workup

  1. customreaction temperature
  2. temperatureincreased to 29° C. due to an exotherm
  3. customreaction mixture
  4. customwas placed into water bath
  5. customthe temperature below 30° C.
  6. customReaction
  7. stirringwas stirred for 16 h (RT)
  8. temperaturethe reaction mixture was heated to 32° C.
  9. stirringstirred for another 5 h
  10. customhad been consumed
  11. customReaction
  12. customwas quenched
  13. additionby adding 10 g of glacial acetic acid
  14. stirringby stirring for 30 min
  15. customReaction mixture
  16. filtrationwas filtered through celite
  17. filtrationfilter cake
  18. washwas washed with THF
  19. concentrationFiltrate was concentrated

Sources & evidence

ORD record
ord-ea617781b5f04a72ade4e57479fe175f
Source dataset
uspto-grants-2014_03
Patent number
US08673897B2

Reaction notes

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