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

HRID 409572ノート

反応式

HRID 409572 の反応式
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

参加物

7

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 1140Toluene溶媒

反応条件

温度
80 °C

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-6a62205f7ccd411683336d78312ae61f
出典データセット
uspto-grants-2014_06
特許番号
US08759387B2

反応ノート

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