Methyl iodide → (2S,4R)-2-methyl 1-(2-(trimethylsilyl)ethyl) 4-(4'-(dimethylamino)-2'-vinylbiphenyl-4-yl)-4-methoxypyrrolidine-1,2-dicarboxylate

HRID 1043440Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1043440
[H-].[Na+].[CH3:3][N:4]([CH3:38])[C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][C:14]([C@@:17]3([OH:35])[CH2:21][N:20]([C:22]([O:24][CH2:25][CH2:26][Si:27]([CH3:30])([CH3:29])[CH3:28])=[O:23])[C@H:19]([C:31]([O:33][CH3:34])=[O:32])[CH2:18]3)=[CH:13][CH:12]=2)=[C:7]([CH:36]=[CH2:37])[CH:6]=1.[CH3:39]I>CN(C=O)C>[CH3:38][N:4]([CH3:3])[C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:12]=[CH:13][C:14]([C@@:17]3([O:35][CH3:39])[CH2:21][N:20]([C:22]([O:24][CH2:25][CH2:26][Si:27]([CH3:29])([CH3:30])[CH3:28])=[O:23])[C@H:19]([C:31]([O:33][CH3:34])=[O:32])[CH2:18]3)=[CH:15][CH:16]=2)=[C:7]([CH:36]=[CH2:37])[CH:6]=1

Komponenten

5

Edukt 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 59266521(2S,4R)-2-methyl 1-(2-(trimethylsilyl)ethyl) 4-(4'-(dimethylamino)-2'-vinylbiphenyl-4-yl)-4-hydroxypyrrolidine-1,2-dicarboxylate

Produkt 1

HCID 59266572(2S,4R)-2-methyl 1-(2-(trimethylsilyl)ethyl) 4-(4'-(dimethylamino)-2'-vinylbiphenyl-4-yl)-4-methoxypyrrolidine-1,2-dicarboxylateAusbeute 68,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

NaH (60% in oil) (46 mg, 1.163 mmol) was added to a solution of (2S,4R)-2-methyl 1-(2-(trimethylsilyl)ethyl) 4-(4′-(dimethylamino)-2′-vinylbiphenyl-4-yl)-4-hydroxypyrrolidine-1,2-dicarboxylate (330 mg, 0.646 mmol) and methyl iodide (0.073 mL, 1.163 mmol) at 0° C. in DMF and stirred at this temperature and allowed to warm up to r.t. overnight. The reaction was then quenched with saturated 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 (5-45% EtOAc in hexanes) to give the semi purified (2S,4R)-2-methyl 1-(2-(trimethylsilyl)ethyl) 4-(4′-(dimethylamino)-2′-vinylbiphenyl-4-yl)-4-methoxypyrrolidine-1,2-dicarboxylate (231 mg, 0.440 mmol, 68% yield) as a clear oil. LCMS: rt=1.86 min. [M+H]+=525; 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.

Aufarbeitung

  1. customThe reaction was then quenched with saturated 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 (5-45% EtOAc in hexanes)
  8. customto give the semi

Quellen und Nachweise

ORD-Eintrag
ord-79c1ca2cf08a4068a1946c0a8e544573
Quelldatensatz
uspto-grants-2013_10
Patentnummer
US08563505B2

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