Methanol → Hydroxylamine

HRID 383457Notes

Reaction equation

HRID 383457 reaction equation
[CH3:1][C:2]1[C:6]([C:7]2[N:8]([C:19]3[CH:24]=[CH:23][C:22]([OH:25])=[CH:21][CH:20]=3)[C:9]3[C:14]([C:15]=2[C:16](Cl)=[O:17])=[CH:13][CH:12]=[CH:11][CH:10]=3)=[C:5]([CH3:26])[O:4][N:3]=1.Cl.NO.[OH-:30].[K+].[CH3:32]O>>[NH2:3][OH:4].[CH3:1][C:2]1[C:6]([C:7]2[N:8]([C:19]3[CH:24]=[CH:23][C:22]([OH:25])=[CH:21][CH:20]=3)[C:9]3[C:14]([C:15]=2[C:16]([O:30][CH3:32])=[O:17])=[CH:13][CH:12]=[CH:11][CH:10]=3)=[C:5]([CH3:26])[O:4][N:3]=1

Participants

6

Reactant 4

HCID 887Methanol3×HCID 14797Potassium HydroxideHCID 443297Hydroxyamine hydrochlorideHCID 58378221HCID 58378221, compound

Product 2

HCID 787HydroxylamineHCID 44466108HCID 44466108, compound

Procedure

2-(3,5-Dimethylisoxazol-4-yl)-1-(4-hydroxyphenyl)-1H-indole-3-carbonyl chloride was dissolved in 0.5 ml of dry MeOH and the mixture was cooled on an ice-bath. Fresh hydroxylamine was prepared by pouring a MeOH solution (0.3 ml) of hydroxylamine hydrochloride (12 mg, 0.17 mmol) into a MeOH solution (0.3 ml) of KOH (19 mg, 0.33 mmol). The mixture was filtered through a syringe filter into the cooled acid chloride solution. After 5 min, the cooling bath was removed and the reaction was allowed to warm to RT and was stirred for 10 min Water, 1M HCl and EtOAc were added and the phases were separated. After evaporation of the solvents, the residue was purified by preparative HPLC to provide methyl 2-(3,5-dimethylisoxazol-4-yl)-1-(4-hydroxyphenyl)-1H-indole-3-carboxylate in 16% yield. ES/MS m/z: 363.11 (M+H), 361.13 (M−H); 1H NMR (methanol-d4, 500 MHz): 8.21 (m, 1H), 7.32-7.26 (m, 2H), 7.20 (m, 1H), 7.13 (br s, 1H), 7.01 (br s, 1H), 6.88 (m, 2H), 3.83 (s, 3H), 2.12 (s, 3H) and 2.03 (s, 3H).

Workup

  1. temperaturethe mixture was cooled on an ice-bath
  2. filtrationThe mixture was filtered through a syringe
  3. filtrationfilter into the cooled acid chloride solution
  4. customthe cooling bath was removed
  5. additionwere added
  6. customthe phases were separated
  7. customAfter evaporation of the solvents
  8. customthe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-a57da272cc6a4e7486ac9fbbea198033
Source dataset
uspto-grants-2013_02
Patent number
US08367665B2

Reaction notes

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