Reaktion #163420

Reaktionsgleichung

oxalyl chloride

triethylamine

oxalyl chloride

N-(3-acetylamino-2-hydroxypropyl)acetamide

1-(3′,4′-Dichloro-2-fluorobiphenyl-4-yl)cyclopropanecarboxylic acid

→

title compound

1-(3′,4′-Dichloro-2-fluorobiphenyl-4-yl)cyclopropane carboxylic acid 2-acetylamino-1-(acetylaminomethyl)-ethyl ester

Lösungsmittel

DCM

DMF

DCM

pyridine

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGthe reaction was stirred for 15 minutes
2. 2
   Sonstigesynthesized
3. 3
   workup.STIRRINGthe reaction mixture was stirred overnight at r.t
4. 4
   ExtraktionThe reaction mixture was extracted with DCM/H2O
5. 5
   Waschenthe organic phase was washed with brine
6. 6
   Trocknendried over sodium sulphate
7. 7
   Filtrationfiltered
8. 8
   Sonstigeevaporated to dryness
9. 9
   SonstigeThe residue was purified by gradient flash chromatography (eluent DCM to DCM/methanol 97/3 v/v)

Vorschrift

1-(3′,4′-Dichloro-2-fluorobiphenyl-4-yl)cyclopropanecarboxylic acid (0.30 g, 0.92 mmol) was dissolved in dry DCM (30 mL); two drops of DMF and oxalyl chloride (78 uL, 0.92 mmol) were added; and the reaction mixture was stirred at r.t. under nitrogen atmosphere for 30 minutes. Additional oxalyl chloride (39 uL, 0.46 mmol) was added and the reaction was stirred for 15 minutes. This solution was added dropwise to a solution of N-(3-acetylamino-2-hydroxypropyl)acetamide (synthesized as reported on J. Org. Chem., 2000, 65(4), 1200, which is incorporated herein by reference in its entirety) and triethylamine (385 uL, 2.76 mmol) in dry DCM (2 mL) and dry DMF (2 mL). 4-Dimethylaminopyridine (34 mg, 0.28 mmol) and dry pyridine (1.5 mL) were added, and the reaction mixture was stirred overnight at r.t. The reaction mixture was extracted with DCM/H2O, and the organic phase was washed with brine, dried over sodium sulphate, filtered and evaporated to dryness. The residue was purified by gradient flash chromatography (eluent DCM to DCM/methanol 97/3 v/v) affording the title compound which was further purified by preparative HPLC to obtain 1-(3′,4′-dichloro-2-fluorobiphenyl-4-yl)cyclopropanecarboxylic acid 2-acetylamino-1-(acetylaminomethyl)ethyl ester (105 mg, 24% yield) as a white solid.

Quelle