Ethyl Acetate → Tert-butyl 3-[(5-bromo-4-methyl-2H-indazol-2-yl)methyl]-azetidin-1-carboxylate

HRID 2174927Notes

Reaction equation

HRID 2174927 reaction equation
[Br:1][C:2]1[C:3]([CH3:11])=[C:4]2[C:8](=[CH:9][CH:10]=1)[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[Si]([N-][Si](C)(C)C)(C)C.[Na+].C(OCC)(=O)C>O1CCOCC1.O1CCCC1.O>[Br:1][C:2]1[CH:10]=[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)[C:3]=1[CH3:11]

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 2724254Sodium bis(trimethylsilyl)amideHCID 441192325-Bromo-4-methyl-1H-indazoleHCID 56777214Tert-butyl 3-(tosyloxymethyl)azetidine-1-carboxylate

Product 1

HCID 117690535Tert-butyl 3-[(5-bromo-4-methyl-2H-indazol-2-yl)methyl]-azetidin-1-carboxylate

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 21.1 g of 5-bromo-4-methyl-1H-indazole and 37.6 g of tert-butyl-3-[(tosyloxy)-methyl]azetidin-1-carboxylate in 100 ml dioxan were added 150 ml of a 1M solution of sodium bis(trimethylsilyl)amide in tetrahydrofuran at 25° C. and this was stirred for 6 hrs at 90° C. After cooling, the reaction mixture was treated with ethyl acetate and water, the organic phases separated and the aqueous phase extracted twice with 100 ml portions of ethyl acetate. The combined organic phases were washed with saturated sodium chloride solution, dried over sodium sulphate, and concentrated in vacuo after filtration.

Workup

  1. temperatureAfter cooling
  2. customthe organic phases separated
  3. extractionthe aqueous phase extracted twice with 100 ml portions of ethyl acetate
  4. washThe combined organic phases were washed with saturated sodium chloride solution
  5. dry with materialdried over sodium sulphate
  6. concentrationconcentrated in vacuo
  7. filtrationafter filtration

Sources & evidence

ORD record
ord-20781fbff8cc45bc8a8d2d772b8723e5
Source dataset
uspto-grants-2015_06
Patent number
US09062041B2

Reaction notes

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