Dimethylformamide → 2-Amino-4-chloro-3,5-difluorobenzaldehyde

HRID 413042Notes

Reaction equation

HRID 413042 reaction equation
C([Li])CCC.Br[C:7]1[CH:13]=[C:12]([F:14])[C:11]([Cl:15])=[C:10]([F:16])[C:8]=1[NH2:9].CN(C)[CH:19]=[O:20].[Cl-].[NH4+]>O1CCCC1>[NH2:9][C:8]1[C:10]([F:16])=[C:11]([Cl:15])[C:12]([F:14])=[CH:13][C:7]=1[CH:19]=[O:20]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 25517Ammonium ChlorideHCID 27732546-Bromo-3-chloro-2,4-difluoroanilineHCID 178418339Butyllithium

Product 1

HCID 185232552-Amino-4-chloro-3,5-difluorobenzaldehyde

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-75 °C

Procedure

66 cm3 of a 2 N butyllithium solution (in hexane) was added dropwise over 30 minutes to a stirred solution of 13.4 g of 2-bromo-5-chloro-4,6-difluoroaniline in 150 cm3 of anhydrous tetrahydrofuran (THF) cooled to a temperature in the region of −75° C. After stirring for 1 hour at this temperature, 12.8 cm3 of dimethylformamide was added. After the addition, the mixture was again stirred for 3 hours at a temperature in the region of −70° C. The mixture was brought to a temperature in the region of −5° C., and then an aqueous ammonium chloride solution (18 g dissolved in 180 cm3) was added. The reaction mixture was extracted twice with 200 cm of diethyl ether. The combined ethereal extracts were washed once with 150 cm3 of water and once with 150 cm3 of a saturated aqueous sodium chloride solution. After drying over magnesium sulphate, the solution was concentrated under reduced pressure (5 kPa), at a temperature in the region of 40° C. After taking up the solid residue obtained in 80 cm3 of hexane and then filtration, 6.2 g of 2-amino-4-chloro-3,5-difluorobenzaldehyde was obtained in the form of a yellow solid.

Workup

  1. additionwas added
  2. additionAfter the addition
  3. customwas brought to a temperature in the region of −5° C.
  4. extractionThe reaction mixture was extracted twice with 200 cm of diethyl ether
  5. washThe combined ethereal extracts were washed once with 150 cm3 of water and once with 150 cm3 of a saturated aqueous sodium chloride solution
  6. dry with materialAfter drying over magnesium sulphate
  7. concentrationthe solution was concentrated under reduced pressure (5 kPa), at a temperature in the region of 40° C
  8. customobtained in 80 cm3 of hexane
  9. filtrationfiltration

Sources & evidence

ORD record
ord-783ef24bebeb4f4da11c27fa097d7783
Source dataset
uspto-grants-2003_05
Patent number
US06566362B2

Reaction notes

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