Phenyl chloroformate → 4-(2-Fluoro-4-nitrophenoxy)-2-[(4-hydroxypiperidin-1-yl)carbonylamino]pyridine

HRID 492670Notes

Reaction equation

HRID 492670 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-:17])=[O:16])=[CH:11][C:10]=2[F:18])[CH:5]=[CH:4][N:3]=1.Cl[C:20](OC1C=CC=CC=1)=[O:21].[OH:29][CH:30]1[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]1.[Cl-].[NH4+]>O1CCCC1.CN(C)C=O.C(N(CC)CC)C>[F:18][C:10]1[CH:11]=[C:12]([N+:15]([O-:17])=[O:16])[CH:13]=[CH:14][C:9]=1[O:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([NH:1][C:20]([N:33]2[CH2:34][CH2:35][CH:30]([OH:29])[CH2:31][CH2:32]2)=[O:21])[CH:7]=1

Participants

8

Reactant 4

HCID 15891Phenyl chloroformateHCID 25517Ammonium ChlorideHCID 79341Piperidin-4-olHCID 231531982-Amino-4-(2-fluoro-4-nitrophenoxy)pyridine

Product 1

HCID 231532844-(2-Fluoro-4-nitrophenoxy)-2-[(4-hydroxypiperidin-1-yl)carbonylamino]pyridineYield 90%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Procedure

2-Amino-4-(2-fluoro-4-nitrophenoxy)pyridine (124.6 mg) was dissolved in tetrahydrofuran (2.5 ml) under a nitrogen atmosphere, and then triethylamine (0.105 ml) and phenyl chloroformate (0.094 ml) were added dropwise thereto while cooling in an ice bath, followed by stirring at room temperature for 1 hr. The reaction mixture was concentrated under a reduced pressure to give a residue, which was dissolved in N,N-dimethylformamide (1.25 ml), and then 4-hydroxypiperidine (253 mg) was added thereto at room temperature, followed by stirring for 2 hrs. To the reaction mixture was added a saturated aqueous solution of ammonium chloride, followed by extracting with ethyl acetate. The organic layer was washed with a saturated aqueous solution of ammonium chloride 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=1:2 to 1:4, then ethyl acetate) to provide the titled compound (169 mg, 90%) as pale yellow powder.

Workup

  1. temperaturewhile cooling in an ice bath
  2. concentrationThe reaction mixture was concentrated under a reduced pressure
  3. customto give a residue, which
  4. customat room temperature
  5. stirringby stirring for 2 hrs
  6. extractionby extracting with ethyl acetate
  7. washThe organic layer was washed with a saturated aqueous solution of ammonium chloride and brine in this order
  8. dry with materialdried over anhydrous sodium sulfate
  9. customThe solvent was evaporated under a reduced pressure
  10. customto give a residue, which
  11. customwas then purified by silica gel column chromatography (eluent

Sources & evidence

ORD record
ord-c82fad9cf5c44f4d947d22393b903311
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

Loading…