Phenylboronic Acid → Isopropyl 5-[acetyl-(3,5-bistrifluoromethylbenzyl)amino]-8-phenyl-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate

HRID 2353875Notes

Reaction equation

HRID 2353875 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].[C:38]1(B(O)O)[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1.[F-].[K+]>O1CCCC1.C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[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]([C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)[CH:34]=[CH:33][C:9]1=2)(=[O:32])[CH3:31]

Participants

8

Reactant 4

HCID 66827Phenylboronic Acid2×HCID 522689Potassium Fluoride2×HCID 27342162-(Dicyclohexylphosphino)biphenyl2×HCID 59003154Isopropyl 5-[acetyl-(3,5-bistrifluoromethylbenzyl)amino]-8-bromo-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate

Product 1

HCID 59003148Isopropyl 5-[acetyl-(3,5-bistrifluoromethylbenzyl)amino]-8-phenyl-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylateYield 73%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalyst2×HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Add a solution of isopropyl-5-[acetyl-(3,5-bistrifluoromethylbenzyl)amino]-8-bromo-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate (0.080 g, 0.134 mmol) in tetrahydrofuran (1 mL) to phenylboronic acid (0.024 g, 0.202 mmol), palladium acetate (0.0015 g, 0.0067 mmol), 2-(dicyclohexylphosphino)biphenyl (0.0047 g, 0.013 mmol) and potassium fluoride (0.023 g, 0.403 mmol) and purge with nitrogen and stir for 2 h at room temperature, then at 50° C. for 12 h. After this initial period, additional phenylboronic acid (0.024 g, 0.202 mol), palladium acetate (0.0015 g, 0.0067 mmol), 2-(dicyclohexylphosphino)biphenyl (0.0047 g, 0.013 mmol) and potassium fluoride (0.023 g, 0.403 mmol) is added and the reaction is heated at 50° C. for 1 h. Cool the reaction to room temperature and dilute with ethyl acetate (30 mL) and wash with 2 N sodium hydroxide and brine (10 mL each). Dry the organic layer over sodium sulfate, filter and remove the solvent under reduced pressure. Purify the residue using chromatography on silica gel, eluting with hexanes/ethyl acetate (60:40), to provide the title compound as a white solid (0.058 g, 72%): ESI MS 593 (M+H).

Workup

  1. custompurge with nitrogen
  2. waitat 50° C. for 12 h
  3. temperaturethe reaction is heated at 50° C. for 1 h
  4. temperatureCool
  5. customthe reaction to room temperature
  6. washwash with 2 N sodium hydroxide and brine (10 mL each)
  7. dry with materialDry the organic layer over sodium sulfate
  8. filtrationfilter
  9. customremove the solvent under reduced pressure
  10. customPurify the residue
  11. washeluting with hexanes/ethyl acetate (60:40)

Sources & evidence

ORD record
ord-cb66cc1488e547a98bf98d7a3ba0edaa
Source dataset
uspto-grants-2010_07
Patent number
US07749992B2

Reaction notes

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