Reaktion #163423

Reaktionsgleichung

N-[3-(acetylmethylamino)-2-hydroxypropyl]-N-methylacetamide

triethylamine

1-(3′,4′-dichloro-2-fluorobiphenyl-4-yl)cyclopropane carboxylic acid

oxalyl dichloride

→

acetic acid 1-[(acetylmethylamino)methyl]-2-{[1-(3′,4′-dichloro-2-fluorobiphenyl-4-yl)cyclopropanecarbonyl]methylamino}ethyl ester

Ausbeute 21.0%

Lösungsmittel

DCM

DCM

DCM

DCM

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeSolvent was evaporated
2. 2
   Sonstigedried under vacuum
3. 3
   Sonstigeobtaining crude acyl chloride
4. 4
   workup.STIRRINGThe reaction was stirred at r.t. overnight
5. 5
   Temperaturheated at 40° C. for 2 hours
6. 6
   Waschenwashed with H2O (2×)
7. 7
   TrocknenThe organic layer was dried with Na2SO4
8. 8
   Filtrationfiltered
9. 9
   Einengenconcentrated to dryness
10. 10
    SonstigeThe crude thus obtained
11. 11
    Sonstigewas purified by silica gel flash chromatography (DCM:methanol 99:1 v/v)

Vorschrift

To a suspension of 1-(3′,4′-dichloro-2-fluorobiphenyl-4-yl)cyclopropane carboxylic acid (1630 mg, 5.012 mmol) in DCM (55 mL) containing a few drops of DMF, under nitrogen atmosphere, at 0° C., oxalyl dichloride (0.849 mL, 10.02 mmol) was added dropwise, and the reaction was stirred at room temperature for 20 minutes. Solvent was evaporated, and the residue taken up with toluene and dried under vacuum, obtaining crude acyl chloride. Acyl chloride was dissolved in DCM (10 mL) and added dropwise, at 0° C., under nitrogen atmosphere, to a solution of N-[3-(acetylmethylamino)-2-hydroxypropyl]-N-methylacetamide (I5) (676 mg, 3.342 mmol) and triethylamine (2.8 mL, 20.08 mmol) in DCM (50 mL). The reaction was stirred at r.t. overnight and then heated at 40° C. for 2 hours. The reaction mixture was diluted with DCM and washed with H2O (2×) and a saturated solution of NaHCO3 (2×). The organic layer was dried with Na2SO4, filtered and concentrated to dryness. The crude thus obtained was purified by silica gel flash chromatography (DCM:methanol 99:1 v/v) affording acetic acid 1-[(acetylmethylamino)methyl]-2-{[1-(3′,4′-dichloro-2-fluorobiphenyl-4-yl)cyclopropanecarbonyl]methylamino}ethyl ester (350 mg, 21% yield) as pale yellow foam.

Quelle