Cesium carbonate → HCID 89814029, compound

HRID 525352Notes

Reaction equation

HRID 525352 reaction equation
I[C:2]1[CH:20]=[CH:19][C:5]([C:6]([NH:8][C:9]2[CH:10]=[CH:11][CH:12]=[C:13]3[C:18]=2[N:17]=[CH:16][CH:15]=[CH:14]3)=[O:7])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].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.[F:69][C:70]1[CH:75]=[CH:74][CH:73]=[CH:72][C:71]=1[CH:76]1[C:80]([CH3:82])([CH3:81])[O:79][C:78](=[O:83])[NH:77]1>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:69][C:70]1[CH:75]=[CH:74][CH:73]=[CH:72][C:71]=1[CH:76]1[C:80]([CH3:81])([CH3:82])[O:79][C:78](=[O:83])[N:77]1[C:2]1[CH:20]=[CH:19][C:5]([C:6]([NH:8][C:9]2[CH:10]=[CH:11][CH:12]=[C:13]3[C:18]=2[N:17]=[CH:16][CH:15]=[CH:14]3)=[O:7])=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 41661718HCID 41661718, compoundHCID 45092074HCID 45092074, compound

Product 1

HCID 89814029HCID 89814029, compoundYield 20%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a nitrogen purged solution of 4-iodo-N-(quinolin-8-yl)benzamide (250 mg, 0.66 mmol) in 1,4-dioxane (5 mL) were added cesium carbonate (435.37 mg, 1.33 mmol), xantphos (77.31 mg, 0.13 mmol), Pd2(dba)3 (61.18 mg, 0.06 mmol) and 4-(2-fluorophenyl)-5,5-dimethyloxazolidin-2-one (167.73 mg, 0.80 mmol). The mixture was purged with nitrogen for 5-10 minutes. The reaction mixture was then stirred for 3 hours at 100° C. After completion of the reaction (monitored by TLC, TLC system: 30% EtOAc in hexane), the reaction mixture was cooled to ambient temperature and filtered through Celite® brand filter aid. The filtrate was concentrated and purified by column chromatography using silica gel and eluting with 30% EtOAc in hexane to afford (R+S) 4-(4-(2-fluorophenyl)-5,5-dimethyl-2-oxooxazolidin-3-yl)-N-(quinolin-8-yl)benzamide (60 mg, 19.71%) as an off-white solid. 1H NMR (400 MHz, DMSO-d6): δ 10.57 (s, 1H), 8.95 (dd, J=1.2 Hz, 1H), 8.68 (d, J=7.6 Hz, 1H), 8.46 (d, J=8.3 Hz, 1H), 8.00-7.95 (m, 2H), 7.82-7.62 (m, 5H), 7.41-7.35 (m, 2H), 7.19-7.08 (m, 2H), 5.84 (s, 1H), 1.69 (s, 3H), 1.03 (s, 3H). m/z (ESI) 456.1 (M+H)+.

Workup

  1. customThe mixture was purged with nitrogen for 5-10 minutes
  2. customAfter completion of the reaction (monitored by TLC, TLC system: 30% EtOAc in hexane)
  3. temperaturethe reaction mixture was cooled to ambient temperature
  4. filtrationfiltered through Celite® brand
  5. filtrationfilter aid
  6. concentrationThe filtrate was concentrated
  7. custompurified by column chromatography
  8. washeluting with 30% EtOAc in hexane

Sources & evidence

ORD record
ord-b62d6e8f49f04daab6485ce0ec7cb122
Source dataset
uspto-grants-2016_05
Patent number
US09340549B2

Reaction notes

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