Magnesium → (2S,4R)-2-methyl 1-(2-(trimethylsilyl)ethyl) 4-(4'-(dimethylamino)-2'-vinylbiphenyl-4-yl)-4-hydroxypyrrolidine-1,2-dicarboxylate

HRID 1043439Notes

Reaction equation

HRID 1043439 reaction equation
[Mg].Br[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][C:12]([N:15]([CH3:17])[CH3:16])=[CH:11][C:10]=2[CH:18]=[CH2:19])=[CH:5][CH:4]=1.[O:20]=[C:21]1[CH2:25][N:24]([C:26]([O:28][CH2:29][CH2:30][Si:31]([CH3:34])([CH3:33])[CH3:32])=[O:27])[C@H:23]([C:35]([O:37][CH3:38])=[O:36])[CH2:22]1>C1COCC1.C(Cl)Cl>[CH3:16][N:15]([CH3:17])[C:12]1[CH:13]=[CH:14][C:9]([C:6]2[CH:7]=[CH:8][C:3]([C@@:21]3([OH:20])[CH2:25][N:24]([C:26]([O:28][CH2:29][CH2:30][Si:31]([CH3:34])([CH3:32])[CH3:33])=[O:27])[C@H:23]([C:35]([O:37][CH3:38])=[O:36])[CH2:22]3)=[CH:4][CH:5]=2)=[C:10]([CH:18]=[CH2:19])[CH:11]=1

Participants

6

Reactant 3

HCID 5462224Magnesium3×HCID 59266363(S)-2-methyl 1-(2-(trimethylsilyl)ethyl) 4-oxopyrrolidine-1,2-dicarboxylateHCID 592665464'-bromo-N,N-dimethyl-2-vinylbiphenyl-4-amine

Product 1

HCID 59266521(2S,4R)-2-methyl 1-(2-(trimethylsilyl)ethyl) 4-(4'-(dimethylamino)-2'-vinylbiphenyl-4-yl)-4-hydroxypyrrolidine-1,2-dicarboxylateYield 27%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Magnesium (62 mg, 2.55 mmol) was stirred in a round bottom flask under N2 for 15 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. 4′-bromo-N,N-dimethyl-2-vinylbiphenyl-4-amine (735 mg, 2.432 mmol) in THF (20 mL), was added 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 (699 mg, 2.432 mmol) in DCM (20 mL) at r.t. 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 (10-40% EtOAc:Hex) to give (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, 27% yield) as a yellow foam. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 0.04 (s, 9H) 0.99-1.11 (m, 2H) 2.34-2.52 (m, 1H) 2.62-2.81 (m, 1H) 3.00-3.07 (m, 6H) 3.68-3.81 (m, 1H) 3.82-3.89 (m, 3H) 4.17-4.34 (m, 3H) 4.49-4.68 (m, 1H) 5.19 (dd, J=11.04, 1.25 Hz, 1H) 5.70 (dd, J=17.57, 1.25 Hz, 1H) 6.67-6.80 (m, 2H) 6.96 (d, J=2.26 Hz, 1H) 7.16-7.22 (m, 1H) 7.34 (m, 2H) 7.49 (m, J=8.28 Hz, 2H). LCMS: rt=1.71 min. [M+H]+=511; 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 sat. 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 (10-40% EtOAc:Hex)

Sources & evidence

ORD record
ord-dde881d310ac46ee82507a877d229d6e
Source dataset
uspto-grants-2013_10
Patent number
US08563505B2

Reaction notes

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