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

HRID 389190Notes

Reaction equation

HRID 389190 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[O:12][CH3:13])[N:8]=[C:7]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[CH:6]=[C:5]2[O:20][C@H:21]1[CH2:25][N:24]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[C@H:23]([C:33]([O:35][CH3:36])=[O:34])[CH2:22]1.[CH:37]([B-](F)(F)F)=[CH2:38].[K+].CCN(CC)CC>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>[CH3:13][O:12][C:11]1[CH:10]=[C:9]2[C:4]([C:5]([O:20][C@H:21]3[CH2:25][N:24]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[C@H:23]([C:33]([O:35][CH3:36])=[O:34])[CH2:22]3)=[CH:6][C:7]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)=[N:8]2)=[CH:3][C:2]=1[CH:37]=[CH2:38]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 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

To a solution of the product from Step 5 (14.0 g, 21.5 mmol) in EtOH (300 mL) was added potassium vinyltrifluoroborate (5.05 g, 37.7 mmol), Et3N (5.25 mL, 37.7 mmol) and PdCl2(dppf)-DCM adduct (1025 mg, 1.26 mmol). The reaction mixture was then heated to reflux for 1.5 hours, cooled to RT, concentrated and partitioned between EtOAc and water. The layers were separated and the organic phase dried over Na2SO4, filtered and concentrated. The residue was purified on silica (gradient elution 10% to 80% EtOAc in hexanes) to give the title compound (10.4 g). LRMS (M+H)+ Calcd.: 505.2; found 505.5.

Workup

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

Sources & evidence

ORD record
ord-98d11b6a5bcf4a3ab3c3b013a21e6d86
Source dataset
uspto-grants-2013_02
Patent number
US08377874B2

Reaction notes

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