Magnesium → (2S,4R)-2-methyl 1-(2-(trimethylsilyl)ethyl) 4-hydroxy-4-(3'-vinylbiphenyl-3-yl)pyrrolidine-1,2-dicarboxylate

HRID 1043430Notes

Reaction equation

HRID 1043430 reaction equation
[Mg].Br[C:3]1[CH:4]=[C:5]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([CH:15]=[CH2:16])[CH:10]=2)[CH:6]=[CH:7][CH:8]=1.[O:17]=[C:18]1[CH2:22][N:21]([C:23]([O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:30])[CH3:29])=[O:24])[C@H:20]([C:32]([O:34][CH3:35])=[O:33])[CH2:19]1>C1COCC1.C(Cl)Cl>[OH:17][C@:18]1([C:3]2[CH:4]=[C:5]([C:9]3[CH:14]=[CH:13][CH:12]=[C:11]([CH:15]=[CH2:16])[CH:10]=3)[CH:6]=[CH:7][CH:8]=2)[CH2:22][N:21]([C:23]([O:25][CH2:26][CH2:27][Si:28]([CH3:30])([CH3:31])[CH3:29])=[O:24])[C@H:20]([C:32]([O:34][CH3:35])=[O:33])[CH2:19]1

Participants

6

Reactant 3

HCID 5462224Magnesium3×HCID 59266363(S)-2-methyl 1-(2-(trimethylsilyl)ethyl) 4-oxopyrrolidine-1,2-dicarboxylateHCID 592665703-Bromo-3'-vinylbiphenyl

Product 1

HCID 59266556(2S,4R)-2-methyl 1-(2-(trimethylsilyl)ethyl) 4-hydroxy-4-(3'-vinylbiphenyl-3-yl)pyrrolidine-1,2-dicarboxylateYield 31%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Magnesium (0.513 g, 21.11 mmol) was stirred in a round bottom flask under nitrogen for 30 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. 3-bromo-3′-vinylbiphenyl (5.21 g, 20.10 mmol) in THF (100 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 (5.78 g, 20.11 mmol) in DCM (110 mL) at 0° C. 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 (5-40% EtOAc:Hex) to give (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, 31% yield) as a yellow foam. 1H NMR (500 MHz, CHLOROFORM-d) δ 0.05 (d, J=2.44 Hz, 9H) 0.99 (dd, J=9.77, 7.32 Hz, 1H) 1.04 (dd, J=9.61, 7.17 Hz, 1H) 1.27 (t, J=7.17 Hz, 1H) 2.38-2.53 (m, 1H) 2.66-2.82 (m, 1H) 3.67-3.83 (m, 1H) 3.82-3.89 (m, 3H) 3.96-4.09 (m, 1H) 4.17-4.32 (m, 2H) 4.52-4.69 (m, 1H) 5.32 (d, J=10.99 Hz, 1H) 5.83 (d, J=17.40 Hz, 1H) 6.80 (dd, J=17.55, 10.83 Hz, 1H) 7.39-7.46 (m, 2H) 7.46-7.52 (m, 3H) 7.55 (ddd, J=4.58, 2.14, 1.83 Hz, 1H) 7.61 (br. s., 1H) 7.73 (s, 1H). LCMS: rt=2.32 min. [M+H]+=468; 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. 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 (5-40% EtOAc:Hex)

Sources & evidence

ORD record
ord-31bca51f4cb54a348df55813560563c9
Source dataset
uspto-grants-2013_10
Patent number
US08563505B2

Reaction notes

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