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Methyl iodide → (2S,4R)-2-methyl 1-(2-(trimethylsilyl)ethyl) 4-methoxy-4-(2-vinylbiphenyl-4-yl)pyrrolidine-1,2-dicarboxylate

HRID 1043418
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HRID 1043418 반응식
[H-].[Na+].[OH:3][C@:4]1([C:22]2[CH:27]=[CH:26][C:25]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[C:24]([CH:34]=[CH2:35])[CH:23]=2)[CH2:8][N:7]([C:9]([O:11][CH2:12][CH2:13][Si:14]([CH3:17])([CH3:16])[CH3:15])=[O:10])[C@H:6]([C:18]([O:20][CH3:21])=[O:19])[CH2:5]1.[CH3:36]I>CN(C=O)C>[CH3:36][O:3][C@:4]1([C:22]2[CH:27]=[CH:26][C:25]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[C:24]([CH:34]=[CH2:35])[CH:23]=2)[CH2:8][N:7]([C:9]([O:11][CH2:12][CH2:13][Si:14]([CH3:17])([CH3:16])[CH3:15])=[O:10])[C@H:6]([C:18]([O:20][CH3:21])=[O:19])[CH2:5]1
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5

반응물 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 59266520(2S,4R)-2-methyl 1-(2-(trimethylsilyl)ethyl) 4-hydroxy-4-(2-vinylbiphenyl-4-yl)pyrrolidine-1,2-dicarboxylate

생성물 1

HCID 59266516(2S,4R)-2-methyl 1-(2-(trimethylsilyl)ethyl) 4-methoxy-4-(2-vinylbiphenyl-4-yl)pyrrolidine-1,2-dicarboxylate수율 31.4%

시약·촉매·용매 1

HCID 6228
Dimethylformamide
용매

실험 절차

NaH (60% in oil) (0.239 g, 5.97 mmol) was added to a solution of (2S,4R)-2-methyl 1-(2-(trimethylsilyl)ethyl) 4-hydroxy-4-(2-vinylbiphenyl-4-yl)pyrrolidine-1,2-dicarboxylate (1.55 g, 3.31 mmol) and methyl iodide (0.373 mL, 5.97 mmol) at 0° C. in DMF and stirred at this temperature for 3 hrs. The reaction was then quenched with sat. NH4Cl solution and ether. The ether layer was washed with brine, dried, filtered and evaporated to give crude material. The crude material was purified by flash chromatography on the Biotage (20-40% EtOAc in hexanes) to give (2S,4R)-2-methyl 1-(2-(trimethylsilyl)ethyl) 4-methoxy-4-(2-vinylbiphenyl-4-yl)pyrrolidine-1,2-dicarboxylate (0.5 g, 1.038 mmol, 31% yield) as a clear oil. LCMS: rt=2.11 min. [M+Na]+=504; Phenomenex-Luna C-18 (5μ) (3.0×50 mm); Solvent A=10% acetonitrile—90% water—0.1% TFA, Solvent B=90% acetonitrile—10% water—0.1% TFA; gradient 0% to 100% solvent B over 2 min. and then hold for 1 min.; 4 mL/min; inj. vol.=5 uL; wavelength=220.

후처리

  1. customThe reaction was then quenched with sat. NH4Cl solution and ether
  2. washThe ether layer was washed with brine
  3. customdried
  4. filtrationfiltered
  5. customevaporated
  6. customto give crude material
  7. customThe crude material was purified by flash chromatography on the Biotage (20-40% EtOAc in hexanes)

출처 및 근거

ORD 기록
ord-f052f94a369a4097ba1b1a9c59228707
출처 데이터셋
uspto-grants-2013_10
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08563505B2

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