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

HRID 1811617Notes

Reaction equation

HRID 1811617 reaction equation
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

Participants

7

Reactant 4

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

Product 1

HCID 11667710(R)-1-(3-methoxyphenyl)ethyl-[(S)-1-(2-trifluoromethylphenyl)pyrrolidin-3-yl]amineYield 43.3%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

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(di-phenylphosphino-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).

Workup

  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)

Sources & evidence

ORD record
ord-7a15bccfd0f44324ab246460421480be
Source dataset
uspto-grants-2013_01
Patent number
US08362274B2

Reaction notes

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