Acetic Acid → HCID 21877054, compound

HRID 723619Notes

Reaction equation

HRID 723619 reaction equation
[CH3:1][CH2:2][C:3](=[O:9])[CH2:4][C:5](=[O:8])[CH2:6][CH3:7].[F:10][C:11]1[CH:18]=[CH:17][CH:16]=[C:15]([F:19])[C:12]=1[CH:13]=O.C(O)(=O)C>N1CCCCC1.C1(C)C=CC=CC=1>[F:10][C:11]1[CH:18]=[CH:17][CH:16]=[C:15]([F:19])[C:12]=1[CH:13]=[C:4]([C:3](=[O:9])[CH2:2][CH3:1])[C:5](=[O:8])[CH2:6][CH3:7]

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 819233,5-HeptanedioneHCID 1362842,6-Difluorobenzaldehyde2×

Product 1

HCID 21877054HCID 21877054, compoundYield 30.7%

Reagents, catalysts & solvents 2

HCID 8082PiperidineCatalystHCID 1140TolueneSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 3,5-heptanedione (1.36 ml, 10 mmol), 2,6-difluorobenzaldehyde (1.08 ml, 10 mmol), piperidine (20 μL, 0.2 mmol), glacial acetic acid (149 μL, 2.6 mmol), molecular sieves and toluene (7 ml) was heated at 70° C., under a nitrogen atmosphere for 3 hours. Further 2,6-difluorobenzaldehyde (540 μL, 5 mmol) was added and the resulting mixture was stirred at 70° C. for a further 7 hours. After cooling, the molecular sieves were filtered off. The filtrate was concentrated under reduced pressure. The residue was partitioned between dichloromethane and water. The organic phase was dried over anhydrous magnesium sulphate, filtered and concentrated under reduced pressure. The crude material was purified by flash chromatography on silica gel eluting with pentane:dichloromethane (4:1, by volume) and then with a solvent gradient of pentane:diethylether (20:1, by volume) gradually changing to pentane:diethylether (10:1, by volume) to afford the title compound (775 mg) as a colourless oil.

Workup

  1. temperatureAfter cooling
  2. filtrationthe molecular sieves were filtered off
  3. concentrationThe filtrate was concentrated under reduced pressure
  4. customThe residue was partitioned between dichloromethane and water
  5. dry with materialThe organic phase was dried over anhydrous magnesium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude material was purified by flash chromatography on silica gel eluting with pentane:dichloromethane (4:1, by volume)

Sources & evidence

ORD record
ord-889fc993a3e846d3bcdc91f48651226c
Source dataset
uspto-grants-2006_11
Patent number
US07141585B2

Reaction notes

Loading…