Allyl Mercaptan → (2S,4R)-1-benzyl 2-methyl 4-(allylthio)-4-(biphenyl-4-yl)pyrrolidine-1,2-dicarboxylate

HRID 1666971ノート

反応式

HRID 1666971 の反応式
[C:1]1([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH:6]=[CH:5][C:4]([C@@:7]2(O)[CH2:11][N:10]([C:12]([O:14][CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[O:13])[C@H:9]([C:22]([O:24][CH3:25])=[O:23])[CH2:8]2)=[CH:3][CH:2]=1.[CH2:33]([SH:36])[CH:34]=[CH2:35]>C(#N)C.FC(F)(F)S([O-])(=O)=O.[Sc+3].FC(F)(F)S([O-])(=O)=O.FC(F)(F)S([O-])(=O)=O>[CH2:33]([S:36][C@:7]1([C:4]2[CH:5]=[CH:6][C:1]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)=[CH:2][CH:3]=2)[CH2:11][N:10]([C:12]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[O:13])[C@H:9]([C:22]([O:24][CH3:25])=[O:23])[CH2:8]1)[CH:34]=[CH2:35]

参加物

5

反応物 2

HCID 13367Allyl MercaptanHCID 59386561HCID 59386561、化合物

生成物 1

HCID 57988337(2S,4R)-1-benzyl 2-methyl 4-(allylthio)-4-(biphenyl-4-yl)pyrrolidine-1,2-dicarboxylate収率 22.15%

試薬・触媒・溶媒 2

HCID 2734571Scandium(III) triflate触媒HCID 6342Acetonitrile溶媒

実験手順

To a clear solution of (2S,4R)-1-benzyl 2-methyl 4-(biphenyl-4-yl)-4-hydroxypyrrolidine-1,2-dicarboxylate (3236 mg, 7.5 mmol) and prop-2-ene-1-thiol (834 mg, 9.00 mmol) in Acetonitrile (40 mL) was added Scandium(III) trifluoromethanesulfonate (369 mg, 0.750 mmol) as solid by one portion at room temperature. The formed pink solution was stirred at this temperature for 20 h. Quenched with sat. ammonium chloride, extracted with EtOAc. Washed the organic layer with brine, dried over MgSO4, filtered, evaporated in vacuo. The residue was purified by Biotage column, eluted with 5%˜50% EtOAc-Hexane to afford a mixture of diastereomers (2.88 g, 79%) and recovered starting material (0.600 g, 18%). This mixture was purified by Biotage column again, eluted with 2%˜8% EtOAc-Toluene to afford the desired product (2S,4R)-1-benzyl 2-methyl 4-(allylthio)-4-(biphenyl-4-yl)pyrrolidine-1,2-dicarboxylate (900 mg, 1.661 mmol, 22.15% yield) as an viscous oil and the undesired diastereomer plus some overlapped fraction (1.80 g) as an viscous oil. 1H NMR (500 MHz, CHLOROFORM-D) δ ppm 2.59-2.75 (m, 1 H), 2.77-2.93 (m, 3 H), 3.60 (s, 1.5 H), 3.77 (s, 1.5 H), 3.92 (d, J=11.60 Hz, 1 H), 4.20-4.30 (m, 1 H), 4.37-4.47 (m, 1 H), 4.92-5.34 (m, 4 H), 5.55-5.72 (m, 1 H), 7.20-7.65 (m, 14 H). LC-MS (retention time: 3.34 min, method B), MS m/z 488 (M+H).

後処理

  1. customQuenched with sat. ammonium chloride
  2. extractionextracted with EtOAc
  3. washWashed the organic layer with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customThe residue was purified by Biotage column
  8. washeluted with 5%˜50% EtOAc-Hexane
  9. customto afford
  10. additiona mixture of diastereomers (2.88 g, 79%)
  11. customrecovered
  12. customThis mixture was purified by Biotage column again
  13. washeluted with 2%˜8% EtOAc-Toluene

出典と根拠

ORDレコード
ord-f9f776341f95446691ae4df825c85dbb
出典データセット
uspto-grants-2011_10
特許番号
US08044087B2

反応ノート

読み込み中…