Acetonitrile → Methyl-9-chloro-5,6-dihydrobenzo[f][1,2,4]triazolo[1,5-d][1,4]oxazepine-2-carboxylate

HRID 886242Notes

Reaction equation

HRID 886242 reaction equation
Br[C:2]1[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][C:3]=1[O:4][CH2:5][CH2:6][N:7]1[CH:11]=[N:10][C:9]([C:12]([O:14][CH3:15])=[O:13])=[N:8]1.C(#N)C.C(=O)([O-])[O-].[Cs+].[Cs+]>[Cl-].C([N+](CC)(CC)CC)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.[Cu]I>[CH3:15][O:14][C:12]([C:9]1[N:10]=[C:11]2[N:7]([CH2:6][CH2:5][O:4][C:3]3[CH:16]=[C:17]([Cl:20])[CH:18]=[CH:19][C:2]=32)[N:8]=1)=[O:13]

Participants

7

Reactant 3

HCID 6342AcetonitrileHCID 10796Cesium carbonateHCID 67050677Methyl 1-[2-(2-bromo-5-chlorophenoxy)ethyl]-1H-1,2,4-triazole-3-carboxylate

Product 1

HCID 58204850Methyl-9-chloro-5,6-dihydrobenzo[f][1,2,4]triazolo[1,5-d][1,4]oxazepine-2-carboxylateYield 15%

Reagents, catalysts & solvents 3

HCID 5946Tetraethylammonium ChlorideCatalystHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
165 °C

Procedure

To methyl 1-(2-(2-bromo-5-chlorophenoxy)ethyl)-1H-1,2,4-triazole-3-carboxylate in acetonitrile (10.00 mL, 191.5 mmol) was added cesium carbonate (0.9036 g, 2.773 mmol) in a microwave flask with stirbar. The mixture was degassed by bubbling nitrogen by syringe. Tetraethylammonium chloride (0.2298 g, 1.387 mmol), palladium acetate (0.1556 g, 0.6933 mmol), and copper(I) iodide (0.02641 g, 0.1387 mmol) were added, respectively, and the vessel was sealed by crimping. Next, the flask was heated while stirring to 165° C. for 18 min in the microwave. Once the reaction was cooled to room temperature, the crude was filtered through celite, concentrated, and purified by silica gel chromatography, to give Methyl-9-chloro-5,6-dihydrobenzo[f][1,2,4]triazolo[1,5-d][1,4]oxazepine-2-carboxylate in 15% yield. 1H NMR (400 MHz, CDCl3) δ 8.59 (d, J=2.6 Hz, 1H), 7.34 (dd, J=8.8, 2.7 Hz, 1H), 7.04 (d, J=8.8 Hz, 1H), 4.75 (m, 2H), 4.53 (m, 2H), 4.05 (s, 3H). LRMS m/z Calcd. for C12H10ClN3O3: 279.04107, found: 280.0 [M+1]

Workup

  1. customThe mixture was degassed
  2. customby bubbling nitrogen by syringe
  3. customrespectively, and the vessel was sealed by crimping
  4. temperatureNext, the flask was heated
  5. temperatureOnce the reaction was cooled to room temperature
  6. filtrationthe crude was filtered through celite,
  7. concentrationconcentrated
  8. custompurified by silica gel chromatography

Sources & evidence

ORD record
ord-1ab8eb0350f64e79915f5825a158a7dc
Source dataset
uspto-grants-2012_08
Patent number
US08242104B2

Reaction notes

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