Cesium carbonate → Tert-butyl 3-[(5-bromo-6-methyl-2H-indazol-2-yl)methyl]azetidin-1-carboxylate

HRID 2174930Notes

Reaction equation

HRID 2174930 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[CH3:11])[NH:7][N:6]=[CH:5]2.[C:12]([O:16][C:17]([N:19]1[CH2:22][CH:21]([CH2:23]OS(C2C=CC(C)=CC=2)(=O)=O)[CH2:20]1)=[O:18])([CH3:15])([CH3:14])[CH3:13].C(=O)([O-])[O-].[Cs+].[Cs+].CCCCCC.CCOCC>CN(C=O)C.[I-].C([N+](CCCC)(CCCC)CCCC)CCC.O>[Br:1][C:2]1[C:10]([CH3:11])=[CH:9][C:8]2[C:4](=[CH:5][N:6]([CH2:23][CH:21]3[CH2:22][N:19]([C:17]([O:16][C:12]([CH3:13])([CH3:15])[CH3:14])=[O:18])[CH2:20]3)[N:7]=2)[CH:3]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 21584099Diethylether hexaneHCID 247292595-Bromo-6-methyl-1H-indazoleHCID 56777214Tert-butyl 3-(tosyloxymethyl)azetidine-1-carboxylate

Product 1

HCID 117690707Tert-butyl 3-[(5-bromo-6-methyl-2H-indazol-2-yl)methyl]azetidin-1-carboxylate

Reagents, catalysts & solvents 3

HCID 67553Tetrabutylammonium IodideCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 6.18 g of 5-bromo-6-methyl-1H-indazole and 15 g of tert-butyl-3-[(tosyl-oxy)methyl]azetidin-1-carboxylate in 200 ml DMF were added 9.54 g of caesium carbonate and 10.8 g of tetrabutylammonium iodide at 25° C., and this was then heated under reflux for 1.5 hrs. After cooling, the reaction mixture was treated with 1:1 hexane/ether and water, the phases separated and the aqueous phase extracted twice with 250 ml portions of 1:1 hexane/ether. The combined organic phases were washed with saturated sodium chloride solution, dried over sodium sulphate, and concentrated in vacuo after filtration.

Workup

  1. temperaturethis was then heated
  2. temperatureunder reflux for 1.5 hrs
  3. temperatureAfter cooling
  4. customthe phases separated
  5. extractionthe aqueous phase extracted twice with 250 ml portions of 1:1 hexane/ether
  6. washThe combined organic phases were washed with saturated sodium chloride solution
  7. dry with materialdried over sodium sulphate
  8. concentrationconcentrated in vacuo
  9. filtrationafter filtration

Sources & evidence

ORD record
ord-6d6cb6daced64a44a70a9b0e30308d7c
Source dataset
uspto-grants-2015_06
Patent number
US09062041B2

Reaction notes

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