Methylboronic Acid → Isopropyl 5-[acetyl-(3,5-bistrifluoromethylbenzyl)amino]-7,8-dimethyl-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate

HRID 2353892Notes

Reaction equation

HRID 2353892 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]=[C:34](Br)[C:35]([CH3:37])=[CH:36][C:8]1=2)=[O:6])([CH3:3])[CH3:2].[CH3:39]B(O)O.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.O.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[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]=[C:34]([CH3:39])[C:35]([CH3:37])=[CH:36][C:8]1=2)=[O:6])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 139377Methylboronic AcidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 22031701Potassium phosphate, tribasic, monohydrateHCID 59003226Isopropyl-5-[acetyl-(3,5-bistrifluoromethylbenzyl)amino]-7-bromo-8-methyl-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate

Product 1

HCID 59003160Isopropyl 5-[acetyl-(3,5-bistrifluoromethylbenzyl)amino]-7,8-dimethyl-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylateYield 38.7%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Combine isopropyl-5-[acetyl-(3,5-bistrifluoromethylbenzyl)amino]-7-bromo-8-methyl-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate (0.058 g, 0.095 mmol), methylboronic acid (0.011 g, 0.190 mmol), palladium acetate (0.0009 g, 0.004 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (0.0036 g, 0.0087 mmol) and potassium phosphate monohydrate (0.044 g, 0.190 mmol) in toluene (2 mL) and heat in a sealed tube at 100° C. for 24 h. Dilute the cooled mixture with ethyl acetate (30 mL) 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 a white solid (0.020 g, 38%): ESI MS 545 (M+H).

Workup

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

Sources & evidence

ORD record
ord-8cb7203a0bf5471696039892895be68d
Source dataset
uspto-grants-2010_07
Patent number
US07749992B2

Reaction notes

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