Hydrochloric Acid → (R)-1-(3-methoxyphenyl)ethyl-[(S)-1-(2-trifluoromethylphenyl)pyrrolidin-3-yl]amine dihydrochloride

HRID 1811618Notes

Reaction equation

HRID 1811618 reaction equation
[Ca].[CH3:2][O:3][C:4]1[CH:5]=[C:6]([C@H:10]([NH:12][C@H:13]2[CH2:17][CH2:16][N:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[C:24]([F:27])([F:26])[F:25])[CH2:14]2)[CH3:11])[CH:7]=[CH:8][CH:9]=1.[ClH:28].O1CCOCC1>C(Cl)(Cl)Cl>[ClH:28].[ClH:28].[CH3:2][O:3][C:4]1[CH:5]=[C:6]([C@H:10]([NH:12][C@H:13]2[CH2:17][CH2:16][N:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[C:24]([F:26])([F:27])[F:25])[CH2:14]2)[CH3:11])[CH:7]=[CH:8][CH:9]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 5460341CalciumHCID 11667710(R)-1-(3-methoxyphenyl)ethyl-[(S)-1-(2-trifluoromethylphenyl)pyrrolidin-3-yl]amine

Product 1

HCID 67408320(R)-1-(3-methoxyphenyl)ethyl-[(S)-1-(2-trifluoromethylphenyl)pyrrolidin-3-yl]amine dihydrochloride

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

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. additionwas added to the mixture
  2. customThe reaction mixture was evaporated
  3. additiondiethyl ether was added to the residue
  4. filtrationthe precipitates were collected by filtration
  5. washwashed with diethyl ether

Sources & evidence

ORD record
ord-04e2d01bfcac4cc39e9a77796b1165bf
Source dataset
uspto-grants-2013_01
Patent number
US08362274B2

Reaction notes

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