Phenyl chloroformate → HCID 23153594, compound

HRID 492686Notes

Reaction equation

HRID 492686 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][C:12]([N+:15]([O-])=O)=[CH:11][C:10]=2[Cl:18])[N:5]=[CH:4][N:3]=1.Cl[C:20](OC1C=CC=CC=1)=[O:21].[NH:29]1[CH2:33][CH2:32][CH2:31][CH2:30]1.[Cl-].[NH4+]>O1CCCC1.[Fe].O.C(O)C.C(N(CC)CC)C>[NH2:15][C:12]1[CH:13]=[CH:14][C:9]([O:8][C:6]2[CH:7]=[C:2]([NH:1][C:20]([N:29]3[CH2:33][CH2:32][CH2:31][CH2:30]3)=[O:21])[N:3]=[CH:4][N:5]=2)=[C:10]([Cl:18])[CH:11]=1

Participants

10

Reactant 4

HCID 15891Phenyl chloroformateHCID 25517Ammonium ChlorideHCID 31268PyrrolidineHCID 57677586HCID 57677586, compound

Product 1

HCID 23153594HCID 23153594, compoundYield 51%

Reagents, catalysts & solvents 5

HCID 23925IronCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Procedure

4-Amino-6-(2-chloro-4-nitropenoxy)pyrimidine (230 mg) was dissolved in tetrahydrofuran (5 ml) under a nitrogen atmosphere, and then triethylamine (0.24 ml) and phenyl chloroformate (0.216 ml) were added dropwise thereto while cooling in an ice bath, followed by stirring at room temperature for 1 hr. Pyrrolidine (0.507 ml) was added thereto, followed by stirring for another 1 hr. The reaction mixture was partitioned between ethyl acetate and a saturated aqueous solution of ammonium chloride. The organic layer was washed with a saturated aqueous solution of ammonium chloride, water, a saturated aqueous solution of sodium hydrogencarbonate and brine in this order, and dried over anhydrous sodium sulfate. The solvent was evaporated under a reduced pressure to give a residue, to which ethanol (20 ml)-water (5 ml) was added to dissolve, and then electrolytic iron powder (400 mg) and ammonium chloride (800 mg) were added thereto, followed by heating under reflux for 2 hr. The reaction mixture was cooled down to room temperature, and filtered through celite to remove an insoluble portion, which was washed with ethyl acetate-tetrahydrofuran (1:1) and water. The organic layer of the filtrate was separated, washed with water and brine in this order, and dried over anhydrous sodium sulfate. The solvent was evaporated under a reduced pressure to give a residue, which was then purified by silica gel column chromatography (eluent; hexane:ethyl acetate=1:4, then ethyl acetate) to provide the titled compound (145.5 mg, 51%) as white powder.

Workup

  1. temperaturewhile cooling in an ice bath
  2. stirringby stirring for another 1 hr
  3. customThe reaction mixture was partitioned between ethyl acetate
  4. washThe organic layer was washed with a saturated aqueous solution of ammonium chloride, water
  5. dry with materiala saturated aqueous solution of sodium hydrogencarbonate and brine in this order, and dried over anhydrous sodium sulfate
  6. customThe solvent was evaporated under a reduced pressure
  7. customto give a residue
  8. dissolutionto dissolve
  9. temperatureby heating
  10. temperatureunder reflux for 2 hr
  11. temperatureThe reaction mixture was cooled down to room temperature
  12. filtrationfiltered through celite
  13. customto remove an insoluble portion, which
  14. washwas washed with ethyl acetate-tetrahydrofuran (1:1) and water
  15. customThe organic layer of the filtrate was separated
  16. washwashed with water and brine in this order
  17. dry with materialdried over anhydrous sodium sulfate
  18. customThe solvent was evaporated under a reduced pressure
  19. customto give a residue, which
  20. customwas then purified by silica gel column chromatography (eluent

Sources & evidence

ORD record
ord-f500482d12744586bc4551868b575b0c
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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