Hydroxyamine hydrochloride → 2-bromo-6,7-dihydro-1H-indol-4(5H)-one oxime

HRID 1056164Notes

Reaction equation

HRID 1056164 reaction equation
[Br:1][C:2]1[NH:3][C:4]2[CH2:5][CH2:6][CH2:7][C:8](=O)[C:9]=2[CH:10]=1.Cl.[NH2:13][OH:14].C([O-])(=O)C.[Na+]>CO>[Br:1][C:2]1[NH:3][C:4]2[CH2:5][CH2:6][CH2:7][C:8](=[N:13][OH:14])[C:9]=2[CH:10]=1

Participants

5

Reactant 3

HCID 443297Hydroxyamine hydrochlorideHCID 517045Sodium AcetateHCID 587922772-Bromo-1,5,6,7-tetrahydro-4H-indol-4-one

Product 1

HCID 1371847162-bromo-6,7-dihydro-1H-indol-4(5H)-one oximeYield 114.6%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of 2-bromo-6,7-dihydro-1H-indol-4(5H)-one (303a) (222 mg, 1.04 mmol), hydroxylamine hydrochloride (80 mg, 1.14 mmol), and sodium acetate (94 mg, 1.14 mmol) in MeOH (28 mL) was stirred under argon at 50° C. for 22 h. The reaction mixture was then concentrated in vacuo, and the residue was partitioned between saturated aq. NaHCO3 (40 mL) and EtOAc (60 mL). The organic layer was separated, and the aq. layer was extracted with EtOAc (60 mL). The combined extracts were dried over Na2SO4, filtered, and concentrated in vacuo to provide 2-bromo-6,7-dihydro-1H-indol-4(5H)-one oxime (273 mg) as an off-white solid. 1H NMR (400 MHz, CDCl3) δ ppm: (˜2:1 mixture of oxime isomers) Major isomer: 7.99 (1H, br. s.), 6.36 (1H, br. s.), 2.71 (2H, br. s.), 2.63 (2H, br. s.), 1.89-1.98 (2H, m). Minor isomer: 1H NMR (400 MHz, CDCl3) δ ppm 8.14 (1H, br. s.), 6.97 (1H, br. s.), 2.67-2.75 (2H, m), 2.47 (2H, br. s.), 1.99 (2H, br. s.). m/z (ESI, +ve) 228.9/231.1 (M+H)+.

Workup

  1. concentrationThe reaction mixture was then concentrated in vacuo
  2. customthe residue was partitioned between saturated aq. NaHCO3 (40 mL) and EtOAc (60 mL)
  3. customThe organic layer was separated
  4. extractionthe aq. layer was extracted with EtOAc (60 mL)
  5. dry with materialThe combined extracts were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-83ea7c58938b4862af5173819994b7aa
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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