Cesium carbonate → 3-[(R*)-1-[(S)-1-(2,3-Dihydro-benzo[1,4]dioxin-2-yl)methyl]-piperidin-3-yl]-phenylamine

HRID 453829ノート

反応式

HRID 453829 の反応式
[O:1]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[O:4][CH2:3][C@@H:2]1[CH2:11][N:12]1[CH2:17][CH2:16][CH2:15][C@H:14]([C:18]2[CH:19]=[C:20](OS(C(F)(F)F)(=O)=O)[CH:21]=[CH:22][CH:23]=2)[CH2:13]1.C(=O)([O-])[O-].[Cs+].[Cs+].C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(=[NH:97])(C1C=CC=CC=1)C1C=CC=CC=1.C([O-])(=O)C.[Na+].Cl.NO>O1CCCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[O:1]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[O:4][CH2:3][C@@H:2]1[CH2:11][N:12]1[CH2:17][CH2:16][CH2:15][C@H:14]([C:18]2[CH:19]=[C:20]([NH2:97])[CH:21]=[CH:22][CH:23]=2)[CH2:13]1

参加物

9

反応物 6

HCID 10796Cesium carbonateHCID 136809Benzophenone imineHCID 443297Hydroxyamine hydrochlorideHCID 517045Sodium AcetateHCID 634876Binap, (A+-)-HCID 86644712Trifluoromethanesulfonic acid 3-{(R*)-1-[(S)-1-(2,3-dihydrobenzo[1,4]dioxin-2-yl)methyl]-piperidin-3-yl}phenyl ester

生成物 1

HCID 251762893-[(R*)-1-[(S)-1-(2,3-Dihydro-benzo[1,4]dioxin-2-yl)methyl]-piperidin-3-yl]-phenylamine収率 20.5%

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
80 °C

実験手順

A mixture of trifluoro-methanesulfonic acid 3-{(R*)-1-[(S)-1-(2,3-dihydro-benzo[1,4]dioxin-2-yl)methyl]-piperidin-3-yl}-phenyl ester (1.039 g, 2.27 mmol), cesium carbonate (1.036 g, 3.18 mmol), palladium acetate (0.015, 0.068 mmol), (R)-(+)-2,2-bis(diphenylphosphino)-1,1-binaphthyl (0.064 g, 0.102 mmol) and benzophenone imine (0.457 ml, 2.73 mmol) in dry tetrahydrofuran (6 ml) was heated in a microwave reactor at 80° C. for 10 hours. The mixture was filtered and evaporated to dryness. The crude product was purified by flash chromatography using a gradient of heptane and EtOAc as eluent. The residue on evaporation was dissolved in dry methanol, sodium acetate (0.54 g, 6.55 mmol) and hydroxylamine hydrochloride (0.36 g, 5.24 mmol) was added and the mixture was stirred at room temperature for 1.5 h. The mixture was evaporated to dryness, dissolved in EtOAc and washed with 1M Na2CO3. The organic layer was dried (Na2SO4), filtered and evaporated to dryness. The crude product was purified by flash chromatography using gradient of heptane and EtOAc as eluent to give 151 mg of the title compound.

後処理

  1. filtrationThe mixture was filtered
  2. customevaporated to dryness
  3. customThe crude product was purified by flash chromatography
  4. customThe residue on evaporation
  5. dissolutionwas dissolved in dry methanol
  6. customThe mixture was evaporated to dryness
  7. dissolutiondissolved in EtOAc
  8. washwashed with 1M Na2CO3
  9. dry with materialThe organic layer was dried (Na2SO4)
  10. filtrationfiltered
  11. customevaporated to dryness
  12. customThe crude product was purified by flash chromatography

出典と根拠

ORDレコード
ord-402f1eec099c4737978186db24a4bece
出典データセット
uspto-grants-2013_07
特許番号
US08492549B2

反応ノート

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