Cesium carbonate → (E)-6-methoxy-5-(4-methylpiperidin-1-yl)-2-(4-((trifluoromethyl)thio)benzylidene)-2,3-dihydro-1H-inden-1-one

HRID 2199820Notes

Reaction equation

HRID 2199820 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[O:11][CH3:12])[C:7](=[O:13])/[C:6](=[CH:14]/[C:15]1[CH:20]=[CH:19][C:18]([S:21][C:22]([F:25])([F:24])[F:23])=[CH:17][CH:16]=1)/[CH2:5]2.[CH3:26][CH:27]1[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]1.C(=O)([O-])[O-].[Cs+].[Cs+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>C1(C)C=CC=CC=1.CC(O)(C)C.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]>[CH3:12][O:11][C:10]1[CH:9]=[C:8]2[C:4]([CH2:5]/[C:6](=[CH:14]\[C:15]3[CH:20]=[CH:19][C:18]([S:21][C:22]([F:25])([F:24])[F:23])=[CH:17][CH:16]=3)/[C:7]2=[O:13])=[CH:3][C:2]=1[N:30]1[CH2:31][CH2:32][CH:27]([CH3:26])[CH2:28][CH2:29]1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 693814-MethylpiperidineHCID 634876Binap, (A+-)-HCID 117940068(E)-5-bromo-6-methoxy-2-(4-((trifluoromethyl)thio)benzylidene)-2,3-dihydro-1H-inden-1-one

Product 1

HCID 117940117(E)-6-methoxy-5-(4-methylpiperidin-1-yl)-2-(4-((trifluoromethyl)thio)benzylidene)-2,3-dihydro-1H-inden-1-one

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 6386tert-ButanolSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of 104 (150 mg, 0.348 mmol) and 4-methylpiperidine (69 mg, 0.696 mmol) in toluene and tBuOH (8:2, 10 mL) was added cesium carbonate 228 mg, 0.696). The reaction was degassed and purged with nitrogen for 10 min. Pd2(dba)3 (15.9 mg, 0.0174 mmol) and BINAP (32.4 mg, 0.15 m·mol) was added and again degassed and purged with nitrogen for another 10 min. The reaction was heated to 110° C. for overnight under sealed condition. The reaction was diluted with chloroform and filtered through celite bed. The organic layer was concentrated to get the crude compound 139 which was purified through flash chromatography by using 100-200 mesh silica gel eluting the compound at 10% ethyl acetate in hexane as pale yellow coloured solid (E)-6-methoxy-5-(4-methylpiperidin-1-yl)-2-(4-((trifluoromethyl)thio)benzylidene)-2,3-dihydro-1H-inden-1-one 139.

Workup

  1. customThe reaction was degassed
  2. custompurged with nitrogen for 10 min
  3. customagain degassed
  4. custompurged with nitrogen for another 10 min
  5. customunder sealed condition
  6. additionThe reaction was diluted with chloroform
  7. filtrationfiltered through celite bed
  8. concentrationThe organic layer was concentrated

Sources & evidence

ORD record
ord-d7bfd30d5cfe4bb0a10eac04cba33372
Source dataset
uspto-grants-2016_06
Patent number
US09359315B2

Reaction notes

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