Benzyl chloroformate → HCID 23153029, compound

HRID 492862Notes

Reaction equation

HRID 492862 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][C:12]([NH2:15])=[C:11]([F:16])[CH:10]=2)[N:5]=[CH:4][N:3]=1.C(=O)([O-])O.[Na+].Cl[C:23]([O:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)=[O:24]>CC(C)=O.O>[NH2:1][C:2]1[N:3]=[CH:4][N:5]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:23](=[O:24])[O:25][CH2:26][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)=[C:11]([F:16])[CH:10]=2)[CH:7]=1

Participants

6

Reactant 3

HCID 10387Benzyl chloroformate2×HCID 516892Sodium Bicarbonate2×HCID 23153317HCID 23153317, compound

Product 1

HCID 23153029HCID 23153029, compoundYield 44%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 962WaterSolvent

Procedure

After dissolving 4-amino-6-(4-amino-3-fluorophenoxy)pyrimidine (730 mg) in acetone (60 ml)-water (30 ml), sodium hydrogencarbonate (335 mg) and benzyl chloroformate (0.550 ml) were added while cooling in an ice water bath and the mixture was stirred at the same temperature. After 3.5 hours, sodium hydrogencarbonate (140 mg) and benzyl chloroformate (0.120 ml) were added and stirring was continued for 1 hour. The reaction mixture was concentrated under reduced pressure, ethyl acetate (50 ml)-tetrahydrofuran (100 ml) and saturated aqueous sodium hydrogencarbonate (50 ml) were added to the residue, and the mixture was stirred. The organic layer was separated and washed with a small amount of brine, and then the organic layer was concentrated under reduced pressure. Ethyl acetate (25 ml) was added to the residue and the mixture was stirred. The precipitated insoluble portion was filtered prior to washing with ethyl acetate (5 ml×3). The filtrate was concentrated under reduced pressure and the resultant residue was purified by silica gel column chromatography (eluent; heptane:ethyl acetate=1:2 to 1:4) to provide the title compound (514 mg, 44%) as pale brown powder.

Workup

  1. additionwere added
  2. temperaturewhile cooling in an ice water bath
  3. stirringstirring
  4. waitwas continued for 1 hour
  5. concentrationThe reaction mixture was concentrated under reduced pressure, ethyl acetate (50 ml)-tetrahydrofuran (100 ml) and saturated aqueous sodium hydrogencarbonate (50 ml)
  6. additionwere added to the residue
  7. stirringthe mixture was stirred
  8. customThe organic layer was separated
  9. washwashed with a small amount of brine
  10. concentrationthe organic layer was concentrated under reduced pressure
  11. additionEthyl acetate (25 ml) was added to the residue
  12. stirringthe mixture was stirred
  13. filtrationThe precipitated insoluble portion was filtered
  14. washto washing with ethyl acetate (5 ml×3)
  15. concentrationThe filtrate was concentrated under reduced pressure
  16. customthe resultant residue was purified by silica gel column chromatography (eluent; heptane:ethyl acetate=1:2 to 1:4)

Sources & evidence

ORD record
ord-e1c07002bdeb422b8ceb3891d4f0f0f4
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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