Binap, (A+-)- → 5-(1-Benzyl-pyrrolidin-3-ylamino)-7-methyl-2-(4-trifluoromethoxy-benzyl)-2,3-dihydro-isoindol-1-one

HRID 252072ノート

反応式

HRID 252072 の反応式
[NH2:1][CH:2]1[CH2:6][CH2:5][N:4]([CH2:7][C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH2:3]1.Br[C:15]1[CH:16]=[C:17]2[C:21](=[C:22]([CH3:24])[CH:23]=1)[C:20](=[O:25])[N:19]([CH2:26][C:27]1[CH:32]=[CH:31][C:30]([O:33][C:34]([F:37])([F:36])[F:35])=[CH:29][CH:28]=1)[CH2:18]2.CC([O-])(C)C.[Na+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>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.[Pd].[Pd].O>[CH2:7]([N:4]1[CH2:5][CH2:6][CH:2]([NH:1][C:15]2[CH:16]=[C:17]3[C:21](=[C:22]([CH3:24])[CH:23]=2)[C:20](=[O:25])[N:19]([CH2:26][C:27]2[CH:32]=[CH:31][C:30]([O:33][C:34]([F:37])([F:36])[F:35])=[CH:29][CH:28]=2)[CH2:18]3)[CH2:3]1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1

参加物

8

反応物 4

HCID 634876Binap, (A+-)-HCID 27566131-Benzyl-3-aminopyrrolidineHCID 11560384HCID 11560384、化合物HCID 23676156Sodium t-butoxide

生成物 1

HCID 160396405-(1-Benzyl-pyrrolidin-3-ylamino)-7-methyl-2-(4-trifluoromethoxy-benzyl)-2,3-dihydro-isoindol-1-one収率 70.2%

試薬・触媒・溶媒 3

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 962Water溶媒HCID 1140Toluene溶媒

実験手順

3-Amino-1-benzyl-pyrrolidine (57 mg, 0.325 mmol), 5-Bromo-7-methyl-2-(4-trifluoromethoxybenzyl)-2,3-dihydro-isoindol-1-one (100 mg, 0.25 mmol), NaOtBu (168 mg, 1.75 mmol), BINAP (16 mg, 0.025 mmol) and Pd2(dba)3 (23 mg, 0.025 mmol) were dissolved in anhydrous toluene (5 mL). The mixture was immersed in a 110° C. oil bath. After eighteen hours, the reaction was cooled and poured into water and extracted with ethyl acetate. The organic phase was washed with brine, dried over MgSO4, filtered and concentrated. The compound was purified by column chromatography (50% EtOAc/Hexanes) to provide the title compound as a yellow gum (87 mg, 70%). 1H NMR (300 MHz, CDCl3): δ 7.24-7.34 (m, 7H), 7.18 (d, 2H), 6.34 (d, 2H), 4.72 (s, 2H), 4.33 (d, 1H), 4.12 (s, 2H), 4.04 (m, 1H), 3.64 (collapsed dd, 2H), 2.75-2.83 (m, 2H), 2.66 (s, 3H), 2.58 (dd, 1H), 2.45 (ddd, 1H), 2.32-2.42 (m, 1H), 1.67-1.70 (m, 1H).

後処理

  1. customwas immersed in a 110° C.
  2. waitAfter eighteen hours
  3. temperaturethe reaction was cooled
  4. extractionextracted with ethyl acetate
  5. washThe organic phase was washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe compound was purified by column chromatography (50% EtOAc/Hexanes)

出典と根拠

ORDレコード
ord-cdffd6ba1c894c9b926f45bba62ca1db
出典データセット
uspto-grants-2011_01
特許番号
US07868008B2

反応ノート

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