4-Fluoroaniline → HCID 136041782, compound

HRID 880136Notes

Reaction equation

HRID 880136 reaction equation
[Cl-].[Cl-].[Cl-].[Al+3].[F:5][C:6]1[CH:12]=[CH:11][C:9]([NH2:10])=[CH:8][CH:7]=1.[F:13][C:14]([F:40])([C:20]1[N:25]=[C:24]([O:26]C(OC(C)(C)C)=O)[CH:23]=[C:22]([N:34]2[CH2:39][CH2:38][O:37][CH2:36][CH2:35]2)[N:21]=1)[C:15](OCC)=[O:16].P([O-])(O)(O)=O.[K+]>C1(C)C=CC=CC=1.O>[F:40][C:14]([F:13])([C:20]1[NH:25][C:24](=[O:26])[CH:23]=[C:22]([N:34]2[CH2:39][CH2:38][O:37][CH2:36][CH2:35]2)[N:21]=1)[C:15]([NH:10][C:9]1[CH:11]=[CH:12][C:6]([F:5])=[CH:7][CH:8]=1)=[O:16]

Participants

7

Reactant 4

HCID 97314-FluoroanilineHCID 516951Monobasic potassium phosphateHCID 6451240Aluminum(III) ChlorideHCID 70807227HCID 70807227, compound

Product 1

HCID 136041782HCID 136041782, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent3×

Conditions

Temperature
40 °C

Procedure

0.756 ml of a solution of aluminium trichloride (2N) in toluene are added slowly to a solution of 0.136 ml of 4-fluoroaniline in 5 ml of toluene at a temperature of between 0° C. and 10° C. After stirring for 40 min at a temperature in the region of 20° C., 271 mg of ethyl difluoro[4-({[(2-methylpropan-2-yl)oxy]carbonyl}oxy)-6-(morpholin-4-yl)pyrimidin-2-yl]acetate solubilized in 6 ml of toluene, are slowly added. After refluxing for 2h30, the temperature returns to a temperature in the region of 20° C. and then, at 0° C., 26 ml of water and 26 ml of a molar solution of potassium dihydrogen phosphate are added and the resulting mixture is extracted with ethyl acetate. The organic phase is washed with a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulphate, filtered and concentrated to dryness under reduced pressure. After silica column purification of the residue, eluent: 95/05 CH2Cl2/MeOH, the solid is taken up with 5 ml of dichloromethane, the mixture is heated at 40° C. for 5 min, and then the temperature is returned to a temperature in the region of 20° C. The insoluble material is spin-filter-dried, and washed by triturating, from 1 ml of dichloromethane, three times, and then dried in a vacuum bell jar. 28 mg of 2,2-difluoro-N-(4-fluorophenyl)-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide are obtained in the form of a white powder, the characteristics of which are the following:

Workup

  1. additionare slowly added
  2. temperatureAfter refluxing for 2h30
  3. extractionthe resulting mixture is extracted with ethyl acetate
  4. washThe organic phase is washed with a saturated aqueous solution of sodium chloride
  5. dry with materialdried over anhydrous magnesium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated to dryness under reduced pressure
  8. customAfter silica column purification of the residue, eluent
  9. customis returned to a temperature in the region of 20° C
  10. customThe insoluble material is spin-filter-dried
  11. washwashed
  12. customby triturating, from 1 ml of dichloromethane, three times
  13. customdried in a vacuum bell jar

Sources & evidence

ORD record
ord-a788eefaeaf64bcdbf0e6040ddf6fe78
Source dataset
uspto-grants-2015_03
Patent number
US08993565B2

Reaction notes

Loading…