4-Fluorophenol → HCID 20872664, compound

HRID 497523Notes

Reaction equation

HRID 497523 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]([C:17]2[C:18](Cl)=[N:19][CH:20]=[C:21]([F:23])[CH:22]=2)=[O:16])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:25][C:26]1[CH:31]=[CH:30][C:29]([OH:32])=[CH:28][CH:27]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]([C:17]2[C:18]([O:32][C:29]3[CH:30]=[CH:31][C:26]([F:25])=[CH:27][CH:28]=3)=[N:19][CH:20]=[C:21]([F:23])[CH:22]=2)=[O:16])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 97324-FluorophenolHCID 10796Cesium carbonateHCID 20872663HCID 20872663, compound

Product 1

HCID 20872664HCID 20872664, compoundYield 53.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-[(2-Chloro-5-fluoro-pyridine-3-carbonyl)-amino]-piperidine-1-carboxylic acid tert-butyl ester (4.0 g, 11.18 mmol) (see Preparation 27), 4-fluorophenol (1.378 g, 12.3 mmol) and caesium carbonate (7.29 g, 33.54 mmol) were stirred in N,N-dimethylformamide (40 ml) at 55° C. under an atmosphere of nitrogen for 18 hours. The reaction mixture was then partitioned between ethyl acetate (50 ml) and water (30 ml) and the organic layer separated. The organic layer was then washed with a saturated aqueous solution of sodium chloride (40 ml), dried over anhydrous magnesium sulphate and the solvent removed in vacuo. The residue was purified by flash column chromatography on silica gel eluting with dichloromethane. The product was finally triturated with diethylether (25 ml) giving 4-{[5-fluoro-2-(4-fluorophenoxy)-pyridine-3-carbonyl]-amino}-piperidine-1-carboxylic acid tert-butyl ester (2.59 g) as a white solid.

Workup

  1. customThe reaction mixture was then partitioned between ethyl acetate (50 ml) and water (30 ml)
  2. customthe organic layer separated
  3. washThe organic layer was then washed with a saturated aqueous solution of sodium chloride (40 ml)
  4. dry with materialdried over anhydrous magnesium sulphate
  5. customthe solvent removed in vacuo
  6. customThe residue was purified by flash column chromatography on silica gel eluting with dichloromethane
  7. customThe product was finally triturated with diethylether (25 ml)

Sources & evidence

ORD record
ord-ac2b7776e153446b9e986539086876f4
Source dataset
uspto-grants-2005_09
Patent number
US06949573B2

Reaction notes

Loading…