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Water → Tert-butyl 4-[(5-bromo-6-methyl-2H-indazol-2-yl)methyl]piperidin-1-carboxylate

HRID 2174926
Notes
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Reaction equation

HRID 2174926 reaction equation
[Br:1][C:2]1[C:3](C)=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][N:6]=[CH:5]2.S(O[CH2:23][CH:24]1[CH2:29][CH2:28][N:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:26][CH2:25]1)(C1C=CC(C)=CC=1)(=O)=O.[C:37](=O)([O-])[O-].[Cs+].[Cs+].O>CN(C=O)C.[I-].C([N+](CCCC)(CCCC)CCCC)CCC.C(OCC)(=O)C>[Br:1][C:2]1[C:10]([CH3:37])=[CH:9][C:8]2[C:4](=[CH:5][N:6]([CH2:23][CH:24]3[CH2:25][CH2:26][N:27]([C:30]([O:32][C:33]([CH3:35])([CH3:34])[CH3:36])=[O:31])[CH2:28][CH2:29]3)[N:7]=2)[CH:3]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 106428511-(tert-Butoxycarbonyl)-4-((p-toluenesulfonyloxy)methyl)piperidineHCID 441192325-Bromo-4-methyl-1H-indazole

Product 1

HCID 117690376Tert-butyl 4-[(5-bromo-6-methyl-2H-indazol-2-yl)methyl]piperidin-1-carboxylate

Reagents, catalysts & solvents 3

HCID 67553
Tetrabutylammonium Iodide
Catalyst
HCID 6228DimethylformamideSolvent
HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

10.0 g (47.4 mmol) of 5-bromo-4-methyl-1H-indazole and 21.0 g (56.9 mmol) of tert-butyl 4-[(tosyloxy)methyl]piperidin-1-carboxylate were dissolved in 726 ml DMF. To this were added 21.0 g (56.9 mmol) of tetrabutylammonium iodide and 18.5 g (56.9 mmol) of caesium carbonate and the reaction mixture was heated under nitrogen at 80° C. for 1.5 hrs. For the work-up, it was treated with water and ethyl acetate, the organic phase separated and the aqueous phase extracted several times with ethyl acetate. The organic phases were washed with saturated sodium chloride solution, dried over sodium sulphate and concentrated in vacuo. After purification by column chromatography, this yielded the title compound in 5 g yield.

Workup

  1. customthe organic phase separated
  2. extractionthe aqueous phase extracted several times with ethyl acetate
  3. washThe organic phases were washed with saturated sodium chloride solution
  4. dry with materialdried over sodium sulphate
  5. concentrationconcentrated in vacuo
  6. customAfter purification by column chromatography

Sources & evidence

ORD record
ord-b0c8f199fd904bceab310c44362716d5
Source dataset
uspto-grants-2015_06
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09062041B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes