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

HRID 2174926Notes

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

Participants

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

customthe organic phase separated
extractionthe aqueous phase extracted several times with ethyl acetate
washThe organic phases were washed with saturated sodium chloride solution
dry with materialdried over sodium sulphate
concentrationconcentrated in vacuo
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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