Water → (R)-3-chloro-N-[1-(4-chlorophenyl)ethyl]-3-methyl-1-(trifluoromethyl)cyclobutanecarboxamide

HRID 1841626Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1841626
[Cl:1][C:2]1([CH3:13])[CH2:5][C:4]([C:9]([F:12])([F:11])[F:10])([C:6]([OH:8])=O)[CH2:3]1.C(=O)([O-])[O-].[Na+].[Na+].[Cl:20][C:21]1[CH:26]=[CH:25][C:24]([C@@H:27]([CH3:29])[NH2:28])=[CH:23][CH:22]=1.O>S(Cl)(Cl)=O.O1CCOCC1.O>[Cl:1][C:2]1([CH3:13])[CH2:3][C:4]([C:9]([F:12])([F:11])[F:10])([C:6]([NH:28][C@@H:27]([C:24]2[CH:25]=[CH:26][C:21]([Cl:20])=[CH:22][CH:23]=2)[CH3:29])=[O:8])[CH2:5]1

Komponenten

7

Edukt 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 1715226(1R)-1-(4-chlorophenyl)ethan-1-amineHCID 109219311-(Trifluoromethyl)-3-chloro-3-methylcyclobutane-1-carboxylic acid

Produkt 1

HCID 23550325(R)-3-chloro-N-[1-(4-chlorophenyl)ethyl]-3-methyl-1-(trifluoromethyl)cyclobutanecarboxamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 24386Thionyl ChlorideLösungsmittelHCID 218864351,4-Dioxane--water (1/1)Lösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

A solution of 0.240 g (1.11 mmol) of 3-chloro-3-methyl-1-(trifluoromethyl)cyclobutane carboxylic acid (prepared according to the method described by H. K. Hall, Jr., E. P. Blanchard Jr. and E. L Martin in Macromolecules 4(2) 142-146 (1971)) in 5 mL thionyl chloride was heated at reflux for 1 h. Solvent was removed in vacuo. The residue was added to a solution of 0.176 g (1.66 mmol) sodium carbonate and 0.172 g (1.11 mmol) (R)-4-chloro-α-methylbenzenemethanamine in 6 mL of 1:1 dioxane-water, pre-cooled to 0° C. After stirring at room temperature overnight, the mixture was poured into 50 mL water and extracted two times with 50 mL ethyl acetate (EtOAc). Drying (magnesium sulfate) and removal of the solvent gave an oil which was chromatographed on silica gel, eluting with 25% hexane-dichloromethane, to afford 43 mg of the cis isomer of the title compound: mp 129-130° C., 1H NMR (CDCl3) δ1.49 (d, 3H), 1.69 (s, 3H), 2.86-2.95 (m, 2H), 2.98-3.05 (m, 2H), 5.05-5.12 (q, 1H), 5.86 (s, 1H), 7.20 (d, 2H), 7.32 (d, 2H), and 77 mg of the trans isomer of the title compound: mp 145-146 C, 1H NMR (CDCl3) 1.54 (d, 3H), 1.74 (s, 3H), 2.79-2.86 (m, 2H), 3.13 (d, 2H), 5.14 (q, 1H), 5.85 (s, 1H), 7.23 (d, 2H), 7.31 (d, 2H).

Aufarbeitung

  1. temperatureat reflux for 1 h
  2. customSolvent was removed in vacuo
  3. extractionextracted two times with 50 mL ethyl acetate (EtOAc)
  4. customDrying
  5. custom(magnesium sulfate) and removal of the solvent
  6. customgave an oil which
  7. customwas chromatographed on silica gel
  8. washeluting with 25% hexane-dichloromethane

Quellen und Nachweise

ORD-Eintrag
ord-590c6092d6c248b9a4efbf023f4a261e
Quelldatensatz
uspto-grants-2004_01
Patentnummer
US06683212B1

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