Dimethylformamide → HCID 18613617, compound

HRID 1264622Notes

Reaction equation

HRID 1264622 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([OH:11])=O)=[CH:4][C:3]=1[N+:12]([O-:14])=[O:13].CN(C)C=O.C(Cl)(=O)C(Cl)=O.[NH2:26][C:27]1[S:31][N:30]=[C:29]([CH3:32])[C:28]=1[Cl:33]>ClC(Cl)C>[Cl:33][C:28]1[C:29]([CH3:32])=[N:30][S:31][C:27]=1[NH:26][C:9](=[O:11])[CH2:8][C:5]1[CH:6]=[CH:7][C:2]([OH:1])=[C:3]([N+:12]([O-:14])=[O:13])[CH:4]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 4473644-Hydroxy-3-nitrophenylacetic acidHCID 112405714-Chloro-3-methyl-1,2-thiazol-5-amine

Product 1

HCID 18613617HCID 18613617, compoundYield 89.1%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent2×

Procedure

4-Hydroxy-3-nitrophenylacetic acid (10 g, 0.05 mol) was suspended in dichloroethane (50 ml) and stirred at room temperature under a nitrogen atmosphere. N,N-Dimethylformamide (0.1 ml) was added followed by dropwise addition of oxalyl chloride (6.77 g, 0.05 mol) over 20 minutes. The mixture was stirred at room temperature for 25 minutes and then at 40° C. for 20 minutes. The reaction mixture was then heated under reflux while a solution of 5-amino-4-chloro-3-methylisotiazole (7.54 g, 0.05 mol) in dichloroethane (30 ml) was added over 30 minutes. The resultant pale orange suspension was stirred at reflux for 2 hours and then cooled to room temperature, to give a precipitate, which was collected by filtration and washed with dichloromethane. The solid was suspended in water (150 ml), treated with 10% (w/v) sodium hydroxide (50 ml) and the resulting red solution was washed with dichloromethane (2×50 ml). The combined washings were extracted with water (50 ml) and the combined aqueous layers were acidified to pH4-5 by addition of concentrated hydrochloric acid (approximately 10 ml). The resultant yellow suspension was filtered and the solid was washed with water and dried under suction to give N-(4-chloro-3-methyl-5-isothiazolyl)-4-hydrox-3-nitrophenylacetamide (14.6 g) as a yellow solid.

Workup

  1. stirringThe mixture was stirred at room temperature for 25 minutes
  2. temperatureThe reaction mixture was then heated
  3. additionwas added over 30 minutes
  4. stirringThe resultant pale orange suspension was stirred
  5. temperatureat reflux for 2 hours
  6. temperaturecooled to room temperature
  7. customto give a precipitate, which
  8. filtrationwas collected by filtration
  9. washwashed with dichloromethane
  10. additiontreated with 10% (w/v) sodium hydroxide (50 ml)
  11. washthe resulting red solution was washed with dichloromethane (2×50 ml)
  12. extractionThe combined washings were extracted with water (50 ml)
  13. additionthe combined aqueous layers were acidified to pH4-5 by addition of concentrated hydrochloric acid (approximately 10 ml)
  14. filtrationThe resultant yellow suspension was filtered
  15. washthe solid was washed with water
  16. customdried under suction

Sources & evidence

ORD record
ord-a39b2df25b3e4289aa1f6ee4b06543c7
Source dataset
uspto-grants-2003_04
Patent number
US06544989B2

Reaction notes

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