Methyl iodide → (2S,4R)-2-methyl 1-(2-(trimethylsilyl)ethyl) 4-methoxy-4-(3'-vinylbiphenyl-3-yl)pyrrolidine-1,2-dicarboxylate

HRID 1043431Notes

Reaction equation

HRID 1043431 reaction equation
[H-].[Na+].[OH:3][C@:4]1([C:22]2[CH:23]=[C:24]([C:28]3[CH:33]=[CH:32][CH:31]=[C:30]([CH:34]=[CH2:35])[CH:29]=3)[CH:25]=[CH:26][CH:27]=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:23]=[C:24]([C:28]3[CH:33]=[CH:32][CH:31]=[C:30]([CH:34]=[CH2:35])[CH:29]=3)[CH:25]=[CH:26][CH:27]=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

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 59266556(2S,4R)-2-methyl 1-(2-(trimethylsilyl)ethyl) 4-hydroxy-4-(3'-vinylbiphenyl-3-yl)pyrrolidine-1,2-dicarboxylate

Product 1

HCID 59266553(2S,4R)-2-methyl 1-(2-(trimethylsilyl)ethyl) 4-methoxy-4-(3'-vinylbiphenyl-3-yl)pyrrolidine-1,2-dicarboxylateYield 77.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

NaH (60% in oil) (0.446 g, 11.16 mmol) was added to a solution of (2S,4R)-2-methyl 1-(2-(trimethylsilyl)ethyl) 4-hydroxy-4-(3′-vinylbiphenyl-3-yl)pyrrolidine-1,2-dicarboxylate (2.9 g, 6.20 mmol) and methyl iodide (0.698 mL, 11.16 mmol) at 0° C. in DMF and stirred at this temperature for 3 hrs. 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 (2S,4R)-2-methyl 1-(2-(trimethylsilyl)ethyl) 4-methoxy-4-(3′-vinylbiphenyl-3-yl)pyrrolidine-1,2-dicarboxylate (2.3 g, 4.78 mmol, 77% yield) as a clear oil. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm −0.04-0.11 (m, 9H) 0.89-1.12 (m, 2H) 2.56 (dd, J=13.18, 8.91 Hz, 1H) 2.86 (t, J=12.67 Hz, 1H) 2.99 (d, J=3.01 Hz, 3H) 3.66-3.92 (m, 1H) 3.79 (d, J=7.03 Hz, 3H) 3.99-4.12 (m, 1H) 4.18-4.29 (m, 2H) 4.44-4.70 (m, 1H) 5.33 (d, J=10.79 Hz, 1H) 5.84 (d, J=16.82 Hz, 1H) 6.80 (dd, J=17.57, 11.04 Hz, 1H) 7.34 (d, J=7.53 Hz, 1H) 7.39-7.52 (m, 4H) 7.53-7.59 (m, 3H). LCMS: rt=2.49 min. [M+H]+=482; 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)

Sources & evidence

ORD record
ord-f973fc870a994795aa4d920c0c6c3d70
Source dataset
uspto-grants-2013_10
Patent number
US08563505B2

Reaction notes

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