Morpholine → HCID 59003214, compound

HRID 2353865Notes

Reaction equation

HRID 2353865 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]=[C:46](Br)[CH:47]=[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]=[CH:47][C:46]([N:7]3[CH2:12][CH2:11][O:10][CH2:9][CH2:8]3)=[CH:45][C:21]1=2)(=[O:44])[CH3:43]

Participants

7

Reactant 3

HCID 8083MorpholineHCID 23676156Sodium t-butoxideHCID 59003133HCID 59003133, compound

Product 1

HCID 59003214HCID 59003214, compoundYield 64.3%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
80 °C

Procedure

Combine tris(dibenzylideneacetone)dipalladium (0) (0.031 g, 0.034 mmol), racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphyl (0.064 g, 0.102 mmol) and sodium t-butoxide (0.045 g, 0.470 mmol) in toluene (2 mL) and purge this suspension with nitrogen at room temperature for 5 min. Add morpholine (0.033 mL, 0.369 mmol) followed by isopropyl-5-[acetyl-(3,5-bistrifluoromethylbenzyl)amino]-7-bromo-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate (0.200 g, 0.336 mmol) and heat this mixture at 80° C. under nitrogen for 1 h. Cool the reaction mixture to room temperature, dilute the mixture with dichloromethane, filter through Celite, and concentrate under reduced pressure. Chromatograph the residue over silica gel, eluting with hexanes/ethyl acetate (20:1 to 1:2), to provide the title compound as an off-white solid (0.130 g, 64%): APCI MS 603 (M+H).

Workup

  1. temperatureCool the reaction mixture to room temperature
  2. filtrationfilter through Celite
  3. concentrationconcentrate under reduced pressure
  4. washChromatograph the residue over silica gel, eluting with hexanes/ethyl acetate (20:1 to 1:2)

Sources & evidence

ORD record
ord-555071f66e55494e8549c236131b92ff
Source dataset
uspto-grants-2010_07
Patent number
US07749992B2

Reaction notes

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