Dimethylformamide → 6-Bromo-5-(2-fluoro-4-nitrophenoxy)-1-methyl-1H-indazole

HRID 2195491Notes

Reaction equation

HRID 2195491 reaction equation
Br[C:2]1[CH:11]=[C:10]([Br:12])[C:9]([O:13][C:14]2[CH:19]=[CH:18][C:17]([N+:20]([O-:22])=[O:21])=[CH:16][C:15]=2[F:23])=[CH:8][C:3]=1[CH:4]=[N:5][NH:6][CH3:7].C(=O)([O-])[O-].[K+].[K+].CN(C=O)C.CC(OC)(C)C>C(Cl)Cl.O>[Br:12][C:10]1[CH:11]=[C:2]2[C:3]([CH:4]=[N:5][N:6]2[CH3:7])=[CH:8][C:9]=1[O:13][C:14]1[CH:19]=[CH:18][C:17]([N+:20]([O-:22])=[O:21])=[CH:16][C:15]=1[F:23]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 15413tert-Butyl methyl etherHCID 667671401-(2,4-Dibromo-5-(2-fluoro-4-nitrophenoxy)benzylidene)-2-methylhydrazine

Product 1

HCID 667668536-Bromo-5-(2-fluoro-4-nitrophenoxy)-1-methyl-1H-indazoleYield 80.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

1-(2,4-Dibromo-5-(2-fluoro-4-nitrophenoxy)benzylidene)-2-methylhydrazine (1.0 g, 2.2 mmol), cuprous chloride (22 mg, 0.2 mmol), potassium carbonate (0.638 g, 7.2 mmol), DMF (10 mL), and a stir bar are combined in a pressure tube under nitrogen. The cap is sealed and the tube is placed in an oil bath with stirring. The bath is heated to 100° C. over 30 min and held at 100° C. for 6 hours and then cooled to RT. The reaction mixture is poured into a separatory funnel containing MTBE (10 mL) and water (10 mL). The layers are separated and the aqueous layer is extracted with an additional portion of MTBE (10 mL). The organic layers are combined, and washed with water followed by saturated sodium chloride aqueous solution. The organic layer is dried over magnesium sulfate and concentrated to yield 0.70 g of crude product. The crude solid is dissolved in DCM and heptane, and then concentrated to remove DCM resulting in the formation of a slurry. The product is collected by filtration and dried under vacuum to give 6-bromo-5-(2-fluoro-4-nitrophenoxy)-1-methyl-1H-indazole as a solid (0.65 g, 79% yield). MS (m/z): 367.8 (M+H).

Workup

  1. customThe cap is sealed
  2. customthe tube is placed in an oil bath
  3. temperaturecooled to RT
  4. additionThe reaction mixture is poured into a separatory funnel
  5. customThe layers are separated
  6. extractionthe aqueous layer is extracted with an additional portion of MTBE (10 mL)
  7. washwashed with water
  8. dry with materialThe organic layer is dried over magnesium sulfate
  9. concentrationconcentrated
  10. customto yield 0.70 g of crude product
  11. concentrationheptane, and then concentrated
  12. customto remove DCM resulting in the formation of a slurry
  13. filtrationThe product is collected by filtration
  14. customdried under vacuum

Sources & evidence

ORD record
ord-48a0aa72c12d4477adbd61124fdff6c5
Source dataset
uspto-grants-2012_12
Patent number
USRE043878E1

Reaction notes

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