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Magnesium → (2S,4R)-2-methyl 1-(2-(trimethylsilyl)ethyl) 4-(5'-chloro-2'-vinylbiphenyl-4-yl)-4-hydroxypyrrolidine-1,2-dicarboxylate

HRID 1043426
ノート
印刷プレビュー

反応式

HRID 1043426 の反応式
[Mg].Br[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[C:13]([Cl:15])[CH:12]=[CH:11][C:10]=2[CH:16]=[CH2:17])=[CH:5][CH:4]=1.[O:18]=[C:19]1[CH2:23][N:22]([C:24]([O:26][CH2:27][CH2:28][Si:29]([CH3:32])([CH3:31])[CH3:30])=[O:25])[C@H:21]([C:33]([O:35][CH3:36])=[O:34])[CH2:20]1>C1COCC1.C(Cl)Cl>[Cl:15][C:13]1[CH:12]=[CH:11][C:10]([CH:16]=[CH2:17])=[C:9]([C:6]2[CH:7]=[CH:8][C:3]([C@@:19]3([OH:18])[CH2:23][N:22]([C:24]([O:26][CH2:27][CH2:28][Si:29]([CH3:32])([CH3:30])[CH3:31])=[O:25])[C@H:21]([C:33]([O:35][CH3:36])=[O:34])[CH2:20]3)=[CH:4][CH:5]=2)[CH:14]=1
参加物実験手順後処理出典と根拠反応ノート

参加物

6

反応物 3

HCID 5462224Magnesium3 回HCID 59266363(S)-2-methyl 1-(2-(trimethylsilyl)ethyl) 4-oxopyrrolidine-1,2-dicarboxylateHCID 592665224'-Bromo-5-chloro-2-vinylbiphenyl

生成物 1

HCID 59266523(2S,4R)-2-methyl 1-(2-(trimethylsilyl)ethyl) 4-(5'-chloro-2'-vinylbiphenyl-4-yl)-4-hydroxypyrrolidine-1,2-dicarboxylate収率 14%

試薬・触媒・溶媒 2

HCID 6344
Dichloromethane
溶媒
HCID 8028Tetrahydrofuran溶媒2 回

実験手順

Magnesium (0.298 g, 12.27 mmol) was stirred in a round bottom flask under nitrogen for 15 min. to cause scratching of the surface of the magnesium turnings. 10 mL of THF was added to the magnesium turnings and stirred for an additional 30 min. 4′-bromo-5-chloro-2-vinylbiphenyl (3.43 g, 11.68 mmol) in THF (60 mL), was added in dropwise at reflux with vigorous stirring. The Grignard solution was added to a solution of (S)-2-methyl 1-(2-(trimethylsilyl)ethyl) 4-oxopyrrolidine-1,2-dicarboxylate (3.35 g, 11.67 mmol) in DCM (60 mL) at r.t. and stirred for 1 hr and then quenched with saturated NH4Cl solution. The aqueous layer was extracted with DCM and the combined organics were dried, filtered and evaporated to give crude material. The crude material was purified by flash chromatography on the Biotage (10-40% EtOAc:Hex) to give (2S,4R)-2-methyl 1-(2-(trimethylsilyl)ethyl) 4-(5′-chloro-2′-vinylbiphenyl-4-yl)-4-hydroxypyrrolidine-1,2-dicarboxylate (800 mg, 1.593 mmol, 14% yield) as a yellow oil. 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 0.04 (s, 9H) 1.03 (dd, j=9.46, 7.63 Hz, 2H) 2.30-2.48 (m, 1H) 2.63-2.79 (m, 1H) 3.77-3.80 (m, 1H) 3.82-3.86 (m, 3H) 3.95-4.05 (m, 1H) 4.16-4.26 (m, 2H) 4.51-4.67 (m, 1H) 5.20 (d, J=11.90 Hz, 1H) 5.67 (d, J=17.40 Hz, 1H) 6.61 (dd, J=17.40, 10.99 Hz, 1H) 7.26-7.35 (m, 4H) 7.49-7.58 (m, 3H).

後処理

  1. temperatureat reflux with vigorous stirring
  2. stirringstirred for 1 hr
  3. customquenched with saturated NH4Cl solution
  4. extractionThe aqueous layer was extracted with DCM
  5. customthe combined organics were dried
  6. filtrationfiltered
  7. customevaporated
  8. customto give crude material
  9. customThe crude material was purified by flash chromatography on the Biotage (10-40% EtOAc:Hex)

出典と根拠

ORDレコード
ord-65d2ee8843f744c3aafd2735a2002595
出典データセット
uspto-grants-2013_10
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08563505B2

反応ノート

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