Potassium Carbonate → Isopropyl 5-[acetyl-(3,5-bistrifluoromethylbenzyl)amino]-8-methyl-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate

HRID 2353880Notes

Reaction equation

HRID 2353880 reaction equation
[CH:1]([O:4][C:5]([N:7]1[CH2:13][CH2:12][CH2:11][CH:10]([N:14]([C:30](=[O:32])[CH3:31])[CH2:15][C:16]2[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[C:18]([C:26]([F:29])([F:28])[F:27])[CH:17]=2)[C:9]2[CH:33]=[CH:34][C:35](Br)=[CH:36][C:8]1=2)=[O:6])([CH3:3])[CH3:2].[CH3:38]B1OB(C)OB(C)O1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.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]>[C:30]([N:14]([CH2:15][C:16]1[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[C:18]([C:26]([F:29])([F:28])[F:27])[CH:17]=1)[CH:10]1[CH2:11][CH2:12][CH2:13][N:7]([C:5]([O:4][CH:1]([CH3:3])[CH3:2])=[O:6])[C:8]2[CH:36]=[C:35]([CH3:38])[CH:34]=[CH:33][C:9]1=2)(=[O:32])[CH3:31]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 574072TrimethylboroxineHCID 59003154Isopropyl 5-[acetyl-(3,5-bistrifluoromethylbenzyl)amino]-8-bromo-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate

Product 1

HCID 59003132Isopropyl 5-[acetyl-(3,5-bistrifluoromethylbenzyl)amino]-8-methyl-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylateYield 41.1%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Purge with nitrogen, a suspension of isopropyl-5-[acetyl-(3,5-bistrifluoromethylbenzyl)amino]-8-bromo-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate (0.153 g, 0.257 mmol), trimethylboroxine (36 μl, 0.257 mmol), and potassium carbonate (0.106 g, 0.771 mmol) in N,N-dimethylformamide (2 mL) in a 10 mL microwave vessel. Add tetrakis(triphenylphosphine)palladium (0) (0.030 g, 0.026 mmol) and irradiate the mixture at 150° C. for 20 min (50 W). Dilute the mixture with ethyl acetate (20 mL), wash with water and brine (10 mL each), then dry the organic layer over sodium sulfate, filter and remove the solvent under reduced pressure. Purify the residue first using chromatography on silica gel, eluting with hexanes/ethyl acetate (60:40), to provide the title compound as a white solid (0.056 g, 41%): 531 (M+H).

Workup

  1. customPurge with nitrogen
  2. washwash with water and brine (10 mL each)
  3. dry with materialdry the organic layer over sodium sulfate
  4. filtrationfilter
  5. customremove the solvent under reduced pressure
  6. customPurify the residue
  7. washeluting with hexanes/ethyl acetate (60:40)

Sources & evidence

ORD record
ord-1df0358ce2cd431ba4222bcde5e6bbbe
Source dataset
uspto-grants-2010_07
Patent number
US07749992B2

Reaction notes

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