Benzyl Alcohol → Isopropyl 5-[acetyl-(3,5-bistrifluoromethylbenzyl)amino]-8-benzyloxy-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate

HRID 2353884Notes

Reaction equation

HRID 2353884 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(P(C(C)(C)C)C1C=CC=CC=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C.C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:74]([OH:81])[C:75]1[CH:80]=[CH:79][CH:78]=[CH:77][CH:76]=1>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: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]([O:81][CH2:74][C:75]3[CH:80]=[CH:79][CH:78]=[CH:77][CH:76]=3)[CH:34]=[CH:33][C:9]1=2)(=[O:32])[CH3:31]

Participants

8

Reactant 4

HCID 244Benzyl AlcoholHCID 10796Cesium carbonateHCID 11618717Di-tert-butyl(2',4',6'-tris(propan-2-yl)-(1,1'-biphenyl)-2-yl)phosphaneHCID 59003154Isopropyl 5-[acetyl-(3,5-bistrifluoromethylbenzyl)amino]-8-bromo-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate

Product 1

HCID 59003149Isopropyl 5-[acetyl-(3,5-bistrifluoromethylbenzyl)amino]-8-benzyloxy-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylateYield 52%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Procedure

Combine isopropyl-5-[acetyl-(3,5-bistrifluoromethylbenzyl)amino]-8-bromo-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate (0.100 g, 0.168 mmol), tris(dibenzylideneacetone)dipalladium (0) (0.0031 g, 0.0033 mmol), 2-di-tert-butylphosphino-2′,4′,6′-triisopropylbiphenyl (0.0043 g, 0.010 mmol), cesium carbonate (0.082 g, 0.252 mmol) and benzyl alcohol (0.035 mL, 0.336 mmol) in toluene (0.67 mL) in a sealed tube and heat at 110° C. for 20 h. Dilute the cooled mixture with dichloromethane (50 mL) and filter through Celite. Remove the filtrate solvent under reduced pressure and first purify the residue using chromatography on silica gel, eluting with hexanes/ethyl acetate (60:40), to provide the title compound as a white solid (0.054 g, 52%): ESI MS 623 (M+H).

Workup

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

Sources & evidence

ORD record
ord-45be1d1848ad4419801a433829b70863
Source dataset
uspto-grants-2010_07
Patent number
US07749992B2

Reaction notes

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