Morpholine → Isopropyl 5-[acetyl-(3,5-bistrifluoromethylbenzyl)amino]-8-morpholin-4-yl-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate

HRID 2353882Notes

Reaction equation

HRID 2353882 reaction equation
CC(C)([O-])C.[Na+].[NH:7]1[CH2:12][CH2:11][O:10][CH2:9][CH2:8]1.[CH:13]([O:16][C:17]([N:19]1[CH2:25][CH2:24][CH2:23][CH:22]([N:26]([C:42](=[O:44])[CH3:43])[CH2:27][C:28]2[CH:33]=[C:32]([C:34]([F:37])([F:36])[F:35])[CH:31]=[C:30]([C:38]([F:41])([F:40])[F:39])[CH:29]=2)[C:21]2[CH:45]=[CH:46][C:47](Br)=[CH:48][C:20]1=2)=[O:18])([CH3:15])[CH3:14]>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:42]([N:26]([CH2:27][C:28]1[CH:33]=[C:32]([C:34]([F:37])([F:36])[F:35])[CH:31]=[C:30]([C:38]([F:40])([F:39])[F:41])[CH:29]=1)[CH:22]1[CH2:23][CH2:24][CH2:25][N:19]([C:17]([O:16][CH:13]([CH3:15])[CH3:14])=[O:18])[C:20]2[CH:48]=[C:47]([N:7]3[CH2:12][CH2:11][O:10][CH2:9][CH2:8]3)[CH:46]=[CH:45][C:21]1=2)(=[O:44])[CH3:43]

Participants

7

Reactant 3

HCID 8083MorpholineHCID 23676156Sodium t-butoxideHCID 59003154Isopropyl 5-[acetyl-(3,5-bistrifluoromethylbenzyl)amino]-8-bromo-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate

Product 1

HCID 59003217Isopropyl 5-[acetyl-(3,5-bistrifluoromethylbenzyl)amino]-8-morpholin-4-yl-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Procedure

Combine tris(dibenzylideneacetone)dipalladium (0) (0.015 g, 0.017 mmol), 2,2′-bis(diphenylphosphino)-1,1′-binaphyl (0.031 g, 0.050 mmol) and sodium t-butoxide (0.023 g, 0.235 mmol) in toluene (3 mL) in a 10 mL microwave vessel and purge this suspension with nitrogen at room temperature for 5 min. Add morpholine (0.016 mL, 0.185 mmol) followed by isopropyl-5-[acetyl-(3,5-bistrifluoromethylbenzyl)amino]-8-bromo-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate (0.100 g, 0.168 mmol) and irradiate this mixture at 110° C. for 15 min. Dilute the cooled mixture 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 a yellow solid (0.041 g, 40%): ESI MS 602 (M+H)

Workup

  1. customirradiate this mixture at 110° C. for 15 min
  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-97d58a0d0b054e3ea749a806a412cf95
Source dataset
uspto-grants-2010_07
Patent number
US07749992B2

Reaction notes

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