1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) → 4'-Methyl-5-(2-oxo-2,3-dihydro-indol-1-yl)-biphenyl-3-carboxylic acid methyl ester

HRID 2406897Notes

Reaction equation

[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]([C:22]2[CH:27]=[CH:26][C:25]([CH3:28])=[CH:24][CH:23]=2)[CH:8]=[C:9]([NH:11][C:12](=[O:21])[CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2Br)[CH:10]=1)=[O:4].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]([C:22]2[CH:27]=[CH:26][C:25]([CH3:28])=[CH:24][CH:23]=2)[CH:8]=[C:9]([N:11]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH2:13][C:12]2=[O:21])[CH:10]=1)=[O:4]

Participants

Conditions

Temperature: 100 °C

Procedure

The 5-[2-(2-bromo-phenyl)-acetylamino]-4′-methyl-biphenyl-3-carboxylic acid methyl ester from step 1 was dissolved in toluene (3 mL) and CsCO3 (325 mg, 1 equive.), Pd(OAc)2 (15 mg) and XANTPHOS (59 mg) were added. The reaction mixture was stirred overnight at 100° C., then cooled and partitioned between water and ethyl acetate. The organic layer was separated and concentrated under reduced pressure, and the residue was purified by preparative thin layer chromatography (2:1 hexanes:ethyl acetate) to give 4′-methyl-5-(2-oxo-2,3-dihydro-indol-1-yl)-biphenyl-3-carboxylic acid methyl ester, which was used directly in the next step.

Workup

temperaturecooled
custompartitioned between water and ethyl acetate
customThe organic layer was separated
concentrationconcentrated under reduced pressure
customthe residue was purified by preparative thin layer chromatography (2:1 hexanes:ethyl acetate)

Sources & evidence

ORD record: ord-553b7a82ba394cbf8115306c02d3ca44
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08809402B2

Reaction notes

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