Sodium hydride → Methyl 1-cyclobutyl-1H-indazole-3-carboxylate

HRID 602458Notes

Reaction equation

HRID 602458 reaction equation
[H-].[Na+].[NH:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([C:12]([O:14][CH3:15])=[O:13])=[N:4]1.Br[CH:17]1[CH2:20][CH2:19][CH2:18]1.C(=O)([O-])O.[Na+]>CN(C)C=O>[CH:17]1([N:3]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]([C:12]([O:14][CH3:15])=[O:13])=[N:4]2)[CH2:20][CH2:19][CH2:18]1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 78110BromocyclobutaneHCID 516892Sodium BicarbonateHCID 657476methyl 1H-indazole-3-carboxylate

Product 1

HCID 67269842Methyl 1-cyclobutyl-1H-indazole-3-carboxylateYield 56%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a suspension of sodium hydride (60% in mineral, 817 mg, 20.4 mmol) in N,N-dimethylformamide (30 mL) was added a solution of methyl 1H-indazole-3-carboxylate in N,N-dimethylformamide (20 mL) at room temperature. After stirring for 30 min, bromocyclobutane (3.45 g, 25.5 mmol) was added, and the mixture was stirred at 90° C. for 13 h. After cooling to room temperature, the mixture was poured onto saturated aqueous sodium hydrogencarbonate solution (200 mL), and the aqueous layer was extracted with ethyl acetate/toluene (3:1, 200 mL×2). The combined organic layer was dried over magnesium sulfate, and concentrated under reduced pressure. The residue was chromatographed on a column of silica gel eluting with ethyl acetate/n-hexane (1:6 then 1:5) to give 2.21 g (56%) of the title compound as a colorless oil.

Workup

  1. stirringthe mixture was stirred at 90° C. for 13 h
  2. extractionthe aqueous layer was extracted with ethyl acetate/toluene (3:1, 200 mL×2)
  3. dry with materialThe combined organic layer was dried over magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was chromatographed on a column of silica gel eluting with ethyl acetate/n-hexane (1:6

Sources & evidence

ORD record
ord-fdaf70fe5bff45d8aff3fac391713880
Source dataset
uspto-grants-2011_03
Patent number
US07906532B2

Reaction notes

Loading…