Benzophenone imine → Isopropyl 5-[acetyl-(3,5-bistrifluoromethylbenzyl)amino]-8-(benzhydrylideneamino)-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate

HRID 2353877Notes

Reaction equation

HRID 2353877 reaction equation
CC(C)([O-])C.[Na+].[C:7](=[NH:20])([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[CH:21]([O:24][C:25]([N:27]1[CH2:33][CH2:32][CH2:31][CH:30]([N:34]([C:50](=[O:52])[CH3:51])[CH2:35][C:36]2[CH:41]=[C:40]([C:42]([F:45])([F:44])[F:43])[CH:39]=[C:38]([C:46]([F:49])([F:48])[F:47])[CH:37]=2)[C:29]2[CH:53]=[CH:54][C:55](Br)=[CH:56][C:28]1=2)=[O:26])([CH3:23])[CH3:22]>C1(C)C=CC=CC=1.ClCCl.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]>[C:50]([N:34]([CH2:35][C:36]1[CH:41]=[C:40]([C:42]([F:45])([F:44])[F:43])[CH:39]=[C:38]([C:46]([F:48])([F:47])[F:49])[CH:37]=1)[CH:30]1[CH2:31][CH2:32][CH2:33][N:27]([C:25]([O:24][CH:21]([CH3:23])[CH3:22])=[O:26])[C:28]2[CH:56]=[C:55]([N:20]=[C:7]([C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=3)[C:8]3[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=3)[CH:54]=[CH:53][C:29]1=2)(=[O:52])[CH3:51]

Participants

7

Reactant 3

HCID 136809Benzophenone imineHCID 23676156Sodium t-butoxideHCID 59003154Isopropyl 5-[acetyl-(3,5-bistrifluoromethylbenzyl)amino]-8-bromo-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate

Product 1

HCID 86616066Isopropyl 5-[acetyl-(3,5-bistrifluoromethylbenzyl)amino]-8-(benzhydrylideneamino)-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylateYield 89%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
80 °C

Procedure

Combine tris(dibenzylideneacetone)dipalladium (0) (0.077 g, 0.084 mmol), 2,2′-bis(diphenylphosphino)-1,1′-binaphyl (0.157 g, 0.252 mmol) and sodium t-butoxide (0.113 g, 1.18 mmol) in toluene (5 mL) and purge this suspension with nitrogen at room temperature for 5 min. Add benzophenoneimine (0.155 mL, 0.924 mmol) followed by isopropyl-5-[acetyl-(3,5-bistrifluoromethylbenzyl)amino]-8-bromo-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate (0.500 g, 0.840 mmol) and heat this mixture at 80° C. under nitrogen for 1 h. Cool the mixture to room temperature, dilute with dichloromethane and filter through Celite. Remove the filtrate solvent under reduced pressure and purify the residue using chromatography on silica gel, eluting with hexanes/ethyl acetate (60:40), to provide the title compound as an orange oil (0.520 g, 89%): APCI MS 696 (M+H).

Workup

  1. temperatureCool the mixture to room temperature
  2. filtrationfilter through Celite
  3. customRemove the filtrate solvent under reduced pressure
  4. custompurify the residue
  5. washeluting with hexanes/ethyl acetate (60:40)

Sources & evidence

ORD record
ord-dbc5c494f9044566afbda68b8889ce3e
Source dataset
uspto-grants-2010_07
Patent number
US07749992B2

Reaction notes

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