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

HRID 1043440Notes

Reaction equation

HRID 1043440 reaction equation
[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

Participants

5

Reactant 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

Product 1

HCID 59266572(2S,4R)-2-methyl 1-(2-(trimethylsilyl)ethyl) 4-(4'-(dimethylamino)-2'-vinylbiphenyl-4-yl)-4-methoxypyrrolidine-1,2-dicarboxylateYield 68.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-79c1ca2cf08a4068a1946c0a8e544573
Source dataset
uspto-grants-2013_10
Patent number
US08563505B2

Reaction notes

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