Water → (4R)-1-(tert-Butoxycarbonyl)-4-[(6-methoxy-7-vinylisoquinolin-1-yl)oxy]-proline

HRID 2045705Notes

Reaction equation

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

Participants

Conditions

Temperature: 100 °C

Procedure

TEA (0.24 mL, 1.70 mmol) was added to a solution of (4R)-4-[(7-bromo-6-methoxyisoquinolin-1-yl)oxy]-1-(tert-butoxycarbonyl)-L-proline (560 mg, 1.13 mmol) in EtOH (30 mL). Potassium vinyltrifluoroborate (227 mg, 1.70 mmol) and PdCl2(dppf)-CH2Cl2 adduct (46 mg, 0.06 mmol) were then added, and the reaction mixture was stirred at 100° C. for 18 h. The reaction mixture was worked up with EtOAc and water, 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 (40% EtOAc/hexanes) to yield the title compound as an oil. LRMS (M+H)+=443.4.

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 (40% EtOAc/hexanes)

Sources & evidence

ORD record: ord-ad212ec02b2d46d4b081821a780c8b79
Source dataset: uspto-grants-2013_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08591878B2

Reaction notes

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