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

HRID 62267Notes

Reaction equation

HRID 62267 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][CH:18]=[C:17]([C:21]([F:24])([F:23])[F:22])[CH:16]=1)/[CH2:5]2.[CH3:25][CH:26]1[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]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.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][CH:18]=[C:17]([C:21]([F:24])([F:23])[F:22])[CH:16]=3)/[C:7]2=[O:13])=[CH:3][C:2]=1[N:29]1[CH2:30][CH2:31][CH:26]([CH3:25])[CH2:27][CH2:28]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 693814-MethylpiperidineHCID 634876Binap, (A+-)-HCID 117940380(E)-5-bromo-6-methoxy-2-(3-(trifluoromethyl)benzylidene)-2,3-dihydro-1H-inden-1-one

Product 1

HCID 117940216(E)-6-methoxy-5-(4-methylpiperidin-1-yl)-2-(3-(trifluoromethyl)benzylidene)-2,3-dihydro-1H-inden-1-one

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of 152 (120 mg, 0.3007 mmol) and 4-methylpiperidine 129 (60.2 mg, 0.6015 mmol) in toluene was added cesium carbonate (197.2 mg, 0.6015 mmol). The reaction was degassed and purged with nitrogen for 10 min. Pd2(dba)3 (13.7 mg, 0.0150 mmol) and BINAP (28.1 mg, 0.0451 mmol) was added and again degassed and purged with nitrogen for another 10 min. The reaction was heated to 110° C. overnight under sealed conditions. The reaction was diluted with chloroform and filtered through celite bed. The organic layer was concentrated to get the crude compound 153 which was purified through flash chromatography by using 100-200 mesh silica gel eluting the compound (E)-6-methoxy-5-(4-methylpiperidin-1-yl)-2-(3-(trifluoromethyl)benzylidene)-2,3-dihydro-1H-inden-1-one 153 at 25% ethyl acetate in hexane as pale yellow coloured solid.

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. additionThe reaction was diluted with chloroform
  6. filtrationfiltered through celite bed
  7. concentrationThe organic layer was concentrated

Sources & evidence

ORD record
ord-0a5f74eda87c4de2b4ee47ebe5b5ea20
Source dataset
uspto-grants-2016_09
Patent number
US09446047B2

Reaction notes

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