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

HRID 1043417Notes

Reaction equation

HRID 1043417 reaction equation
[CH:1]([C:3]1[CH:8]=[C:7]([Mg]Br)[CH:6]=[CH:5][C:4]=1[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[CH2:2].BrC1C=CC(C2C=CC=CC=2)=C(C=C)C=1.[Mg].[O:33]=[C:34]1[CH2:38][N:37]([C:39]([O:41][CH2:42][CH2:43][Si:44]([CH3:47])([CH3:46])[CH3:45])=[O:40])[C@H:36]([C:48]([O:50][CH3:51])=[O:49])[CH2:35]1>C1COCC1.C1(C)C=CC=CC=1>[OH:33][C@:34]1([C:7]2[CH:6]=[CH:5][C:4]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)=[C:3]([CH:1]=[CH2:2])[CH:8]=2)[CH2:38][N:37]([C:39]([O:41][CH2:42][CH2:43][Si:44]([CH3:46])([CH3:47])[CH3:45])=[O:40])[C@H:36]([C:48]([O:50][CH3:51])=[O:49])[CH2:35]1

Participants

7

Reactant 4

HCID 5462224MagnesiumHCID 59266363(S)-2-methyl 1-(2-(trimethylsilyl)ethyl) 4-oxopyrrolidine-1,2-dicarboxylateHCID 592665654-Bromo-2-vinylbiphenylHCID 178436727HCID 178436727, compound

Product 1

HCID 59266520(2S,4R)-2-methyl 1-(2-(trimethylsilyl)ethyl) 4-hydroxy-4-(2-vinylbiphenyl-4-yl)pyrrolidine-1,2-dicarboxylateYield 18.2%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

(2-vinylbiphenyl-4-yl)magnesium bromide (2.66 g, 9.38 mmol) solution, made by refluxing Intermediate 7 with 1 eq. of magnesium turnings in THF, was added to a solution of (S)-2-methyl 1-(2-(trimethylsilyl)ethyl) 4-oxopyrrolidine-1,2-dicarboxylate (2.7 g, 9.38 mmol) in toluene (75 mL) at 0° C. and stirred for 1 hr and then quenched with sat. 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 (20-33% EtOAc:Hex) to give (2S,4R)-2-methyl 1-(2-(trimethylsilyl)ethyl) 4-hydroxy-4-(2-vinylbiphenyl-4-yl)pyrrolidine-1,2-dicarboxylate (800 mg, 1.711 mmol, 18% yield). LCMS: rt=1.85 min. [M+Na]+=490; 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. customquenched with sat. NH4Cl solution
  2. extractionThe aqueous layer was extracted with DCM
  3. customthe combined organics were dried
  4. filtrationfiltered
  5. customevaporated
  6. customto give crude material
  7. customThe crude material was purified by flash chromatography on the Biotage (20-33% EtOAc:Hex)

Sources & evidence

ORD record
ord-69401695749b4dc888495a057dc6487c
Source dataset
uspto-grants-2013_10
Patent number
US08563505B2

Reaction notes

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