Sodium t-butoxide → N-[5-[3-[3,5-bis(trifluoromethyl)phenyl]-3-(trifluoromethyl)pyrrolidin-1-yl]indan-1-yl]propanamide

HRID 1776994Notes

Reaction equation

HRID 1776994 reaction equation
[F:1][C:2]([F:23])([F:22])[C:3]1[CH:4]=[C:5]([C:13]2([C:18]([F:21])([F:20])[F:19])[CH2:17][CH2:16][NH:15][CH2:14]2)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.Br[C:25]1[CH:26]=[C:27]2[C:31](=[CH:32][CH:33]=1)[CH:30]([NH:34][C:35](=[O:38])[CH2:36][CH3:37])[CH2:29][CH2:28]2.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.C(OCC)(=O)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].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:12][C:9]([F:10])([F:11])[C:7]1[CH:6]=[C:5]([C:13]2([C:18]([F:21])([F:19])[F:20])[CH2:17][CH2:16][N:15]([C:25]3[CH:26]=[C:27]4[C:31](=[CH:32][CH:33]=3)[CH:30]([NH:34][C:35](=[O:38])[CH2:36][CH3:37])[CH2:29][CH2:28]4)[CH2:14]2)[CH:4]=[C:3]([C:2]([F:22])([F:1])[F:23])[CH:8]=1

Participants

8

Reactant 3

HCID 23676156Sodium t-butoxideHCID 532621863-[3,5-Bis(trifluoromethyl)phenyl]-3-(trifluoromethyl)pyrrolidineHCID 59453384N-(5-bromoindan-1-yl)propionic acid amide

Product 1

HCID 45377922N-[5-[3-[3,5-bis(trifluoromethyl)phenyl]-3-(trifluoromethyl)pyrrolidin-1-yl]indan-1-yl]propanamideYield 72.6%

Reagents, catalysts & solvents 4

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

3-[3,5-bis(trifluoromethyl)phenyl]-3-(trifluoromethyl)pyrrolidine (0.46 g) and N-(5-bromo-2,3-dihydro-1H-inden-1-yl)propanamide (0.35 g) were dissolved in toluene and deaeration procedure was performed three times under argon atmosphere. Sodium tert-butoxide (0.25 g), Xantphos (0.05 g) and tris(dibenzylideneacetone)dipalladium (0) (chloroform adduct) (0.03 g) were added to the mixture and heated and stirred at 100° C. under argon atmosphere for 2 hours. The solution was cooled to room temperature and the reaction liquid was diluted with ethyl acetate followed by washing with water and brine. The organic layer was dried over anhydrous magnesium sulfate. The desiccant was filtered and separated, the solvent was evaporated off under reduced pressure, and the residue was purified by a silica gel chromatography to obtain N-(5-{3-[3,5-bis(trifluoromethyl)phenyl]-3-(trifluoromethyl)pyrrolidin-1-yl}-2,3-dihydro-1H-inden-1-yl)propanamide (0.51 g).

Workup

  1. temperatureheated
  2. temperatureThe solution was cooled to room temperature
  3. customthe reaction liquid
  4. washby washing with water and brine
  5. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  6. filtrationThe desiccant was filtered
  7. customseparated
  8. customthe solvent was evaporated off under reduced pressure
  9. customthe residue was purified by a silica gel chromatography

Sources & evidence

ORD record
ord-d850780e0b2840cdae50c3c465c8a116
Source dataset
uspto-grants-2016_02
Patent number
US09266830B2

Reaction notes

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