Methanol → Isopropyl 5-[acetyl-(3,5-bistrifluoromethylbenzyl)amino]-8-chloro-7-methoxy-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate

HRID 2353888Notes

Reaction equation

HRID 2353888 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]([Cl:37])=[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:69](=O)([O-])[O-:70].[Cs+].[Cs+].CO>C1(C)C=CC=CC=1.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]([Cl:37])[C:34]([O:70][CH3:69])=[CH:33][C:9]1=2)(=[O:32])[CH3:31]

Participants

8

Reactant 4

HCID 887MethanolHCID 10796Cesium carbonateHCID 11618717Di-tert-butyl(2',4',6'-tris(propan-2-yl)-(1,1'-biphenyl)-2-yl)phosphaneHCID 59003215Isopropyl-5-[acetyl-(3,5-bistrifluoromethylbenzyl)amino]-7-bromo-8-chloro-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate

Product 1

HCID 59003162Isopropyl 5-[acetyl-(3,5-bistrifluoromethylbenzyl)amino]-8-chloro-7-methoxy-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylateYield 37%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Combine isopropyl-5-[acetyl-(3,5-bistrifluoromethylbenzyl)amino]-7-bromo-8-chloro-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate (0.050 g, 0.079 mmol), tris(dibenzylideneacetone)dipalladium (0) (0.0014 g, 0.0015 mmol), 2-di-tert-butylphosphino-2′,4′,6′-triisopropylbiphenyl (0.002 g, 0.0047 mmol), cesium carbonate (0.039 g, 0.119 mmol) and methanol (0.016 mL, 0.397 mmol) in toluene (1 mL) in a sealed tube and heat at 110° C. for 24 h. Dilute the cooled mixture with ethyl acetate (25 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 (0.017 g, 37%): ESI MS 581 (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-9098cbdc7e0f4864bc25122caace5e3a
Source dataset
uspto-grants-2010_07
Patent number
US07749992B2

Reaction notes

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