Toluene → N-[(1S)-1-(4-{3-[3,5-bis(trifluoromethyl)phenyl]-3-(trifluoromethyl)pyrrolidin-1-yl)phenyl)-ethyl]cyclopropanecarboxamide

HRID 42630

反応式

HRID 42630 の反応式
Br[C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([NH:10][C:11]([CH:13]2[CH2:15][CH2:14]2)=[O:12])[CH3:9])=[CH:4][CH:3]=1.[F:16][C:17]([F:38])([F:37])[C:18]1[CH:19]=[C:20]([C:28]2([C:33]([F:36])([F:35])[F:34])[CH2:32][CH2:31][NH:30][CH2:29]2)[CH:21]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:23]=1.CC(C)([O-])C.[Na+].C1(C)C=CC=CC=1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C(Cl)(Cl)Cl.[Pd].[Pd].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.C(OCC)(=O)C>[F:26][C:24]([F:25])([F:27])[C:22]1[CH:21]=[C:20]([C:28]2([C:33]([F:36])([F:34])[F:35])[CH2:32][CH2:31][N:30]([C:2]3[CH:7]=[CH:6][C:5]([C@@H:8]([NH:10][C:11]([CH:13]4[CH2:15][CH2:14]4)=[O:12])[CH3:9])=[CH:4][CH:3]=3)[CH2:29]2)[CH:19]=[C:18]([C:17]([F:16])([F:37])[F:38])[CH:23]=1

参加物

8

反応物 4

HCID 1140TolueneHCID 800360N-[(1S)-1-(4-bromophenyl)ethyl]cyclopropanecarboxamideHCID 23676156Sodium t-butoxideHCID 532621863-[3,5-Bis(trifluoromethyl)phenyl]-3-(trifluoromethyl)pyrrolidine

生成物 1

HCID 53261930N-[(1S)-1-(4-{3-[3,5-bis(trifluoromethyl)phenyl]-3-(trifluoromethyl)pyrrolidin-1-yl)phenyl)-ethyl]cyclopropanecarboxamide収率 100%

試薬・触媒・溶媒 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)触媒HCID 11029508Palladium, tris[mu-[(1,2-eta:4,5-eta)-(1E,4E)-1,5-diphenyl-1,4-pentadien-3-one]]di-, compd. with trichloromethane (1:1)触媒HCID 8857Ethyl Acetate溶媒

実験手順

To a reaction vessel, N-[(1S)-1-(4-bromophenyl)ethyl]cyclopropanecarboxamide (134 mg), 3-[3,5-bis(trifluoromethyl)phenyl]-3-(trifluoromethyl)pyrrolidine (211 mg), sodium t-butoxide (96 mg), tris(dibenzylideneacetone)dipalladium(0)-chloroform adduct (10 mg), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (18 mg) and toluene (6 ml) were added, and reacted in a microwave reactor (Initiator™, manufactured by Biotage) for 10 minutes at 120° C. Upon the completion of the reaction, ethyl acetate was added and the precipitates were filtered by using silica gel. The solvent was distilled off under reduced pressure and the residue was purified by silica gel column chromatography to obtain N-[(1S)-1-(4-{3-[3,5-bis-(trifluoromethyl)phenyl]-3-(trifluoromethyl)pyrrolidin-1-yl}phenyl)ethyl]cyclopropanecarboxamide (269 mg). 1H-NMR (CDCl3) as given in Table 2

後処理

  1. customreacted in a microwave reactor (Initiator™, manufactured by Biotage) for 10 minutes at 120° C
  2. additionwas added
  3. filtrationthe precipitates were filtered
  4. distillationThe solvent was distilled off under reduced pressure
  5. customthe residue was purified by silica gel column chromatography

出典と根拠

ORDレコード
ord-f0e75c6ea85a4164a3dc0950d8405866
出典データセット
uspto-grants-2013_09
特許番号
US08536201B2

関連ノート

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