Potassium vinyltrifluoroborate → 1-t-Butyl 2-methyl (2S,4R)-4-[(7-methoxy-2-phenyl-6-vinylquinolin-4-yl)oxy]pyrrolidine-1,2-dicarboxylate

HRID 2045698Notes

Reaction equation

HRID 2045698 reaction equation
[CH:1]([B-](F)(F)F)=[CH2:2].[K+].Br[C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][C:18]=1[O:19][CH3:20])[N:15]=[C:14]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[CH:13]=[C:12]2[O:27][C@H:28]1[CH2:32][N:31]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[C@H:30]([C:40]([O:42][CH3:43])=[O:41])[CH2:29]1>CCO.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[CH3:20][O:19][C:18]1[CH:17]=[C:16]2[C:11]([C:12]([O:27][C@H:28]3[CH2:32][N:31]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[C@H:30]([C:40]([O:42][CH3:43])=[O:41])[CH2:29]3)=[CH:13][C:14]([C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=3)=[N:15]2)=[CH:10][C:9]=1[CH:1]=[CH2:2]

Participants

5

Reactant 2

HCID 23679353Potassium vinyltrifluoroborateHCID 58005143HCID 58005143, compound

Product 1

HCID 595711221-t-Butyl 2-methyl (2S,4R)-4-[(7-methoxy-2-phenyl-6-vinylquinolin-4-yl)oxy]pyrrolidine-1,2-dicarboxylateYield 95.9%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 702EthanolSolvent

Procedure

Potassium vinyltrifluoroborate (5.05 g, 37.7 mmol), TEA (5.25 mL, 37.7 mmol) and PdCl2(dppf)-CH2Cl2 adduct (1025 mg, 1.26 mmol) were added to a solution of the product from step 5 (14.0 g, 21.5 mmol) in EtOH (300 mL). The mixture was then heated to reflux for 1.5 h, at which time LC-MS revealed the disappearance of starting material. The reaction mixture was cooled and concentrated and partitioned between EtOAc and water. The layers were separated, and the organic layer was dried over Na2SO4, filtered and concentrated. The residue was purified on silica gel (gradient elution 10% to 80% EtOAc in hexanes) to give the title compound (10.4 g, 82% yield). LRMS (M+H)+ Calcd.: 505.2; found 505.5.

Workup

  1. temperatureThe mixture was then heated
  2. temperatureto reflux for 1.5 h, at which time LC-MS
  3. temperatureThe reaction mixture was cooled
  4. concentrationconcentrated
  5. custompartitioned between EtOAc and water
  6. customThe layers were separated
  7. dry with materialthe organic layer was dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified on silica gel (gradient elution 10% to 80% EtOAc in hexanes)

Sources & evidence

ORD record
ord-c714fa6c75544bdaa98282d390afbfd4
Source dataset
uspto-grants-2013_11
Patent number
US08591878B2

Reaction notes

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