Water → 1-t-Butyl 2-methyl (2S,4R)-4-[(7-methoxy-3-vinylquinolin-2-yl)oxy]pyrrolidine-1,2-dicarboxylate

HRID 389212Notes

Reaction equation

Br[C:2]1[C:3]([O:14][C@H:15]2[CH2:19][N:18]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[C@H:17]([C:27]([O:29][CH3:30])=[O:28])[CH2:16]2)=[N:4][C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[C:7]([O:12][CH3:13])[CH:6]=2.[CH:31]([B-](F)(F)F)=[CH2:32].[K+].CCOC(C)=O.O>CCO.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C(Cl)Cl.Cl[Pd]Cl.[Fe]>[CH3:13][O:12][C:7]1[CH:6]=[C:5]2[C:10]([CH:11]=[C:2]([CH:31]=[CH2:32])[C:3]([O:14][C@H:15]3[CH2:19][N:18]([C:20]([O:22][C:23]([CH3:24])([CH3:25])[CH3:26])=[O:21])[C@H:17]([C:27]([O:29][CH3:30])=[O:28])[CH2:16]3)=[N:4]2)=[CH:9][CH:8]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of 1-t-butyl 2-methyl (2S,4R)-4-[(3-bromo-7-methoxyquinolin-2-yl)oxy]pyrrolidine-1,2-dicarboxylate (2.0 g, 4.2 mmol) in EtOH (30 mL), TEA (0.87 mL, 6.23 mmol) was added. Potassium vinyltrifluoroborate (0.84 g, 6.23 mmol) and dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (0.17 g, 0.21 mmol) were then added, and the reaction mixture was stirred at 100° C. for 2 hours. The reaction mixture was worked up with EtOAc and H2O, and the layers were separated. The organic layer was washed with brine, dried over MgSO4, filtered and concentrated. The crude material was purified on silica (gradient elution, 0-40% EtOAc/hexanes) to yield the title compound as an oil. LRMS (M+H-tBu)+=373.3.

Workup

customthe layers were separated
washThe organic layer was washed with brine
dry with materialdried over MgSO4
filtrationfiltered
concentrationconcentrated
customThe crude material was purified on silica (gradient elution, 0-40% EtOAc/hexanes)

Sources & evidence

ORD record: ord-89f7089090734751a9c3427e9ec79281
Source dataset: uspto-grants-2013_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08377874B2

Reaction notes

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