Reaction #3098

Reaction equation

diazomethane

Hydrogen chloride

dioxane

oxalyl chloride

2-propylpentanoic acid

→

1-Chloro-3-propyl-2-hexanone

Solvents

DMF

dichloromethane

Conditions

Workup

1. 1
   Temperaturewhile warming to ambient temperature
2. 2
   TemperatureThe mixture was cooled to 0° C.
3. 3
   workup.STIRRINGThe reaction mixture was stirred 18 hours
4. 4
   Temperaturewhile warming to ambient temperature
5. 5
   WashThe reaction mixture was washed with 1M aqueous sodium carbonate solution (30 mL)
6. 6
   Dryingdried over anhydrous sodium sulfate
7. 7
   Filtrationfiltered
8. 8
   Concentrationconcentrated under reduced pressure
9. 9
   workup.DISSOLUTIONThe residue was dissolved in ether (2mL)
10. 10
    Temperaturecooled to 0° C. under a nitrogen atmosphere
11. 11
    workup.STIRRINGThe reaction was stirred 18 hours
12. 12
    Temperaturewhile warming to ambient temperature
13. 13
    ConcentrationThe reaction mixture was concentrated under reduced pressure
14. 14
    Otherthe residual oil was used in the next step without further purification

Procedure

To 2-propylpentanoic acid (156.6 μl, 1.00 mmol) dissolved in anhydrous dichloromethane (2 mL) was added DMF (3 μL, 4 mole %), and the solution was cooled to 0° C. under a nitrogen atmosphere. To the solution was added oxalyl chloride (94.3 μL, 1.08 mmol) dropwise over a few minutes. The reaction was stirred 18 hours while warming to ambient temperature. The mixture was cooled to 0° C. and excess ~0.3M ethereal diazomethane solution was added. The reaction mixture was stirred 18 hours while warming to ambient temperature. The reaction mixture was washed with 1M aqueous sodium carbonate solution (30 mL), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was dissolved in ether (2mL) and cooled to 0° C. under a nitrogen atmosphere. Hydrogen chloride as a 4N solution in dioxane (275 μL, 1.10 mmol) was added dropwise over a few minutes. The reaction was stirred 18 hours while warming to ambient temperature. The reaction mixture was concentrated under reduced pressure and the residual oil was used in the next step without further purification.

Source