Benzene, 1-bromo-2-(trifluoromethyl)- → (R)-1-(3-methoxyphenyl)ethyl-[(S)-1-(2-trifluoromethylphenyl)pyrrolidin-3-yl]amine

HRID 1622167

Reaktionsgleichung

Reaktionsgleichung von HRID 1622167
Cl.Cl.[CH3:3][O:4][C:5]1[CH:6]=[C:7]([C@H:11]([NH:13][C@H:14]2[CH2:18][CH2:17][NH:16][CH2:15]2)[CH3:12])[CH:8]=[CH:9][CH:10]=1.Br[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[C:26]([F:29])([F:28])[F:27].CC(C)([O-])C.[Na+].C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:3][O:4][C:5]1[CH:6]=[C:7]([C@H:11]([NH:13][C@H:14]2[CH2:18][CH2:17][N:16]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[C:26]([F:29])([F:28])[F:27])[CH2:15]2)[CH3:12])[CH:8]=[CH:9][CH:10]=1

Komponenten

7

Edukt 4

HCID 9806Benzene, 1-bromo-2-(trifluoromethyl)-HCID 516892Sodium BicarbonateHCID 23676156Sodium t-butoxideHCID 67408353(S)-3-[(R)-1-(3-methoxyphenyl)ethylamino]pyrrolidine dihydrochloride

Produkt 1

HCID 11667710(R)-1-(3-methoxyphenyl)ethyl-[(S)-1-(2-trifluoromethylphenyl)pyrrolidin-3-yl]amineAusbeute 43,3 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 167845palladium(II) acetateKatalysatorHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

To a suspension of 146.6 mg of (S)-3-[(R)-1-(3-methoxyphenyl)ethylamino]pyrrolidine dihydrochloride, 112.5 mg of 1-bromo-2-trifluoromethylbenzene, 22.5 mg of palladium acetate, and 62.3 mg of BINAP (2,2′-bis(diphenylphosphino-1,1′-binaphthyl)) in 5 ml of toluene was added 336 mg of sodium tert-butoxide, and the mixture was stirred at 80° C. for 16 hours. To the reaction mixture was added a saturated sodium bicarbonate solution, the mixture was stirred and then the liquids were separated. The organic layer was dried and concentrated, and the residue was purified by NH silica gel column chromatography (hexane:ethyl acetate=97:3→80:20) to obtain 78.9 mg of (R)-1-(3-methoxyphenyl)ethyl-[(S)-1-(2-trifluoromethylphenyl)pyrrolidin-3-yl]amine. (2) In 10 ml of chloroform was dissolved 78.9 mg of (R)-1-(3-methoxyphenyl)ethyl-[(S)-1-(2-trifluoromethylphenyl)pyrrolidin-3-yl]amine, and 1 ml solution of 4M hydrochloric acid in a dioxane was added to the mixture and the resulting mixture was stirred. The reaction mixture was evaporated, and diethyl ether was added to the residue, and the precipitates were collected by filtration and washed with diethyl ether to obtain 66.7 mg of (R)-1-(3-methoxyphenyl)ethyl-[(S)-1-(2-trifluoromethylphenyl)pyrrolidin-3-yl]amine dihydrochloride (the following Table A1, Example 1.001).

Aufarbeitung

  1. stirringthe mixture was stirred
  2. customthe liquids were separated
  3. customThe organic layer was dried
  4. concentrationconcentrated
  5. customthe residue was purified by NH silica gel column chromatography (hexane:ethyl acetate=97:3→80:20)

Quellen und Nachweise

ORD-Eintrag
ord-0ee0b350e408497a9a9667a984364118
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08778628B2

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