Phenyl chloroformate → HCID 57677315, compound

HRID 492702Notes

Reaction equation

HRID 492702 reaction equation
[NH2:1][C:2]1[CH:15]=[CH:14][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH2:13])[CH:8]=2)=[CH:4][C:3]=1[Cl:16].Cl[C:18](OC1C=CC=CC=1)=[O:19].Cl.[NH:28]1[CH2:31][CH2:30][CH2:29]1.C(=O)([O-])O.[Na+]>O1CCCC1.C(OCC)C.O.C(OCC)(=O)C.CN(C)C=O.C(N(CC)CC)C>[NH2:1][C:2]1[CH:15]=[CH:14][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH:13][C:18]([N:28]3[CH2:31][CH2:30][CH2:29]3)=[O:19])[CH:8]=2)=[CH:4][C:3]=1[Cl:16]

Participants

11

Reactant 4

HCID 15891Phenyl chloroformate3×HCID 516892Sodium BicarbonateHCID 12308726Azetidine hydrochlorideHCID 229367984-(4-Amino-3-chlorophenoxy)pyridin-2-ylamine

Product 1

HCID 57677315HCID 57677315, compoundYield 48.5%

Reagents, catalysts & solvents 6

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent4×HCID 8857Ethyl AcetateSolvent

Procedure

4-(4-Amino-3-chlorophenoxy)pyridin-2-ylamine (750 mg, 3.18 mmol) was dissolved in tetrahydrofuran (30 ml), and then triethylamine (0.444 ml, 4.77 mmol) was added thereto. Phenyl chloroformate (0.399 ml, 4.77 mmol) was added dropwise thereto while ice-cooling, followed by stirring at room temperature for 5 hrs. Triethylamine (0.222 ml) and phenyl chloroformate (0.200 ml) were further added thereto while ice-cooling, followed by stirring for 40 min. Triethylamine (0.111 ml) and phenyl chloroformate (0.100 ml) were further added thereto while ice-cooling, followed by stirring for 30 min. The reaction mixture was concentrated under a reduced pressure to give a residue, to which N,N-dimethylformamide (10 ml), azetidine hydrochloride (1.49 g, 15.9 mmol) and triethylamine (2.66 ml, 19.1 mmol) were added thereto, followed by stirring at room temperature for 3 hrs. To the reaction mixture were added ethyl acetate (50 ml) and water (20 ml), and was further added a saturated aqueous solution of sodium hydrogencarbonate to partition. The organic layer was washed with brine, and dried over anhydrous sodium sulfate. The solvent was evaporated to give a residue, which was then purified by silica gel column chromatography (hexane:ethyl acetate=1:1, ethyl acetate, then ethyl acetate:methanol=20:1 to 10:1). Fractions containing the target compound were concentrated to give a solid, which was suspended in diethyl ether, filtered, and dried under aeration to provide the titled compound (492 mg, 1.54 mmol, 48.5%) as colorless powder.

Workup

  1. temperaturewhile ice-cooling
  2. temperaturewhile ice-cooling
  3. stirringby stirring for 40 min
  4. temperaturewhile ice-cooling
  5. stirringby stirring for 30 min
  6. concentrationThe reaction mixture was concentrated under a reduced pressure
  7. customto give a residue
  8. stirringby stirring at room temperature for 3 hrs
  9. customto partition
  10. washThe organic layer was washed with brine
  11. dry with materialdried over anhydrous sodium sulfate
  12. customThe solvent was evaporated
  13. customto give a residue, which
  14. customwas then purified by silica gel column chromatography (hexane
  15. additionFractions containing the target compound
  16. concentrationwere concentrated
  17. customto give a solid, which
  18. filtrationfiltered
  19. customdried under aeration

Sources & evidence

ORD record
ord-ccd09cd1588f4f5c9069ff8d9914df58
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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