N-Methoxy-N-methylacetamide → 1-(1H-indazol-6-yl)ethan-1-one

HRID 514359Notes

Reaction equation

HRID 514359 reaction equation
Br[C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][NH:8]2)=[CH:4][CH:3]=1.[Li]CCCC.CON(C)[C:19](=[O:21])[CH3:20]>C1COCC1>[NH:8]1[C:9]2[C:5](=[CH:4][CH:3]=[C:2]([C:19](=[O:21])[CH3:20])[CH:10]=2)[CH:6]=[N:7]1

Participants

5

Reactant 3

HCID 537505N-Methoxy-N-methylacetamideHCID 178424716-Bromo-1H-indazoleHCID 178418339Butyllithium

Product 1

HCID 441192231-(1H-indazol-6-yl)ethan-1-oneYield 9.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 6-bromo-1H-indazole (5.0 g, 25.4 mmol) in 40 mL THF was added dropwise n-BuLi (2.5M, 30 mL, 76.2 mmol) at −65° C., and the mixture was stirred for 2 h. Then, N-methoxy-N-methylacetamide (2.9 g, 27.9 mmol) was added. The reaction mixture was stirred for another 2 h at −65° C., then quenched with 40 mL H2O. The mixture was extracted with EtOAc (3×50 mL). The combined organic layers were washed with 100 mL brine, dried, and concentrated to dryness. The residue was purified by flash column chromatography (PE/EA=40/1) to give the title compound 24-a (370 mg, 9%) as a yellow solid. [M+H] Calc'd for C9H8N2O, 161. Found, 161.

Workup

  1. stirringThe reaction mixture was stirred for another 2 h at −65° C.
  2. customquenched with 40 mL H2O
  3. extractionThe mixture was extracted with EtOAc (3×50 mL)
  4. washThe combined organic layers were washed with 100 mL brine
  5. customdried
  6. concentrationconcentrated to dryness
  7. customThe residue was purified by flash column chromatography (PE/EA=40/1)

Sources & evidence

ORD record
ord-033d4476e2fd4c53aa92e5f4daed7de5
Source dataset
uspto-grants-2015_08
Patent number
US09107916B2

Reaction notes

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