4-(Trifluoromethyl)aniline → (2R,5S)-2,5-bis(4-bromophenyl)-1-(4-(trifluoromethyl)phenyl)pyrrolidine

HRID 2364816Notes

Reaction equation

CS(O[CH:6]([C:22]1[CH:27]=[CH:26][C:25]([Br:28])=[CH:24][CH:23]=1)[CH2:7][CH2:8][CH:9](OS(C)(=O)=O)[C:10]1[CH:15]=[CH:14][C:13]([Br:16])=[CH:12][CH:11]=1)(=O)=O.[F:29][C:30]([F:39])([F:38])[C:31]1[CH:37]=[CH:36][C:34]([NH2:35])=[CH:33][CH:32]=1>CN(C=O)C>[Br:16][C:13]1[CH:14]=[CH:15][C:10]([C@H:9]2[CH2:8][CH2:7][C@@H:6]([C:22]3[CH:27]=[CH:26][C:25]([Br:28])=[CH:24][CH:23]=3)[N:35]2[C:34]2[CH:36]=[CH:37][C:31]([C:30]([F:29])([F:38])[F:39])=[CH:32][CH:33]=2)=[CH:11][CH:12]=1

Participants

Conditions

Temperature: 50 °C

Procedure

The product from Example 42B (11.13 g, 20.0 mmol) and 4-(trifluoromethyl)aniline (Aldrich, 32.2 g, 200 mmol) were combined in DMF (50 mL), stirred at 50° C. under nitrogen for 16 hours, cooled and concentrated. The residue was diluted with ethyl acetate, treated with 1M HCl, stirred for 10 minutes and filtered to remove solids. The organic layer of the filtrate was washed with brine, dried (Na2SO4), filtered and concentrated. The residue was purified by flash chromatography (silica gel, 0 to 1% ethyl acetate/hexane) to give the title compound (1.0 g, 10%) as the second eluting stereoisomer. MS (ESI+) m/z 526 (M+H)+.

Workup

temperaturecooled
concentrationconcentrated
additionThe residue was diluted with ethyl acetate
additiontreated with 1M HCl
stirringstirred for 10 minutes
filtrationfiltered
customto remove solids
washThe organic layer of the filtrate was washed with brine
dry with materialdried (Na2SO4)
filtrationfiltered
concentrationconcentrated
customThe residue was purified by flash chromatography (silica gel, 0 to 1% ethyl acetate/hexane)

Sources & evidence

ORD record: ord-244c07279e27408da124b79483be46e8
Source dataset: uspto-grants-2014_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08691938B2

Reaction notes

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