Hydroxylamine HCl → HCID 136331249, compound

HRID 1257328Notes

Reaction equation

HRID 1257328 reaction equation
[F:1][C:2]([F:23])([F:22])[C:3]1[CH:4]=[C:5]([C:9]2[N:10]=[C:11]([CH2:14][N:15]3[CH:19]=[C:18]([C:20]#[N:21])[CH:17]=[N:16]3)[S:12][CH:13]=2)[CH:6]=[CH:7][CH:8]=1.[Cl-].O[NH3+].[C:27](=[O:30])([O-])[OH:28].[Na+].C(N1C=CN=C1)([N:34]1C=CN=C1)=O.N12CCCN=C1CCCCC2>CS(C)=O.O.O1CCCC1>[F:23][C:2]([F:1])([F:22])[C:3]1[CH:4]=[C:5]([C:9]2[N:10]=[C:11]([CH2:14][N:15]3[CH:19]=[C:18]([C:20]4[NH:34][C:27](=[O:30])[O:28][N:21]=4)[CH:17]=[N:16]3)[S:12][CH:13]=2)[CH:6]=[CH:7][CH:8]=1

Participants

9

Reactant 5

HCID 21645Hydroxylamine HClHCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 516892Sodium BicarbonateHCID 66939550HCID 66939550, compound

Product 1

HCID 136331249HCID 136331249, compoundYield 72.2%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of the compound (501 mg, 1.50 mmol) obtained in Example 18b in dimethylsulfoxide (5 mL) were added hydroxyammonium chloride (1.04 g, 15.0 mmol) and sodium hydrogen carbonate (1.26 g, 15.0 mmol), and the mixture was stirred at 80° C. overnight. The reaction mixture was diluted with water, extracted with ethyl acetate, washed with saturated brine, dried over sodium sulfate, and concentrated under reduced pressure. Tetrahydrofuran (10 mL), 1,1′-carbonyldiimidazole (365 mg, 2.25 mmol) and 1,8-diazabicyclo[5.4.0]undec-7-ene (0.224 mL, 1.5 mmol) were added to the residue, and the mixture was stirred at room temperature for 2.5 hr, and further heated under reflux for 1.5 hr. The reaction mixture was extracted with ethyl acetate, washed successively with 1N hydrochloric acid and saturated brine, dried over sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (carrier: silica gel, eluent: hexane-ethyl acetate) and recrystallized from ethyl acetate-hexane to give the title compound (426 mg, 72%) as colorless crystals.

Workup

  1. extractionextracted with ethyl acetate
  2. washwashed with saturated brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. stirringthe mixture was stirred at room temperature for 2.5 hr
  6. temperaturefurther heated
  7. temperatureunder reflux for 1.5 hr
  8. extractionThe reaction mixture was extracted with ethyl acetate
  9. washwashed successively with 1N hydrochloric acid and saturated brine
  10. dry with materialdried over sodium sulfate
  11. concentrationconcentrated under reduced pressure
  12. customThe residue was purified by column chromatography (carrier: silica gel, eluent: hexane-ethyl acetate)
  13. customrecrystallized from ethyl acetate-hexane

Sources & evidence

ORD record
ord-d0f418d3ac494ee5b07449d0ce963f65
Source dataset
uspto-grants-2013_06
Patent number
US08461348B2

Reaction notes

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