Sodium Nitrate → HCID 90389371, compound

HRID 1526541Notes

Reaction equation

HRID 1526541 reaction equation
[F:1][CH:2]([F:19])[C:3]1([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[C:12]=2[CH3:18])[CH:9]2[CH:7]([CH2:8]2)[O:6][C:5]([NH2:10])=[N:4]1.[N+:20]([O-])([O-:22])=[O:21].[Na+].[O-]P([O-])([O-])=O.[K+].[K+].[K+].C(=O)(O)[O-].[Na+]>S(=O)(=O)(O)O.O.ClCCl>[F:19][CH:2]([F:1])[C:3]1([C:11]2[CH:16]=[C:15]([N+:20]([O-:22])=[O:21])[CH:14]=[C:13]([F:17])[C:12]=2[CH3:18])[CH:9]2[CH:7]([CH2:8]2)[O:6][C:5]([NH2:10])=[N:4]1

Participants

8

Reactant 4

HCID 24268Sodium NitrateHCID 62657Potassium Phosphate, TribasicHCID 516892Sodium BicarbonateHCID 90389292HCID 90389292, compound

Product 1

HCID 90389371HCID 90389371, compoundYield 40.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1118Sulfuric AcidSolventHCID 6344DichloromethaneSolvent

Procedure

5-(Difluoromethyl)-5-(3-fluoro-2-methylphenyl)-2-oxa-4-azabicyclo[4.1.0]hept-3-en-3-amine (0.470 g, 1.739 mmol) was dissolved in sulfuric acid, 95% (5 mL) and cooled in an ice bath. Sodium nitrate (0.177 g, 2.087 mmol) was added in one portion and the reaction stirred for 5 minutes. The reaction was warmed to rt and stirred for 1 hr and poured into a mixture of dichloromethane (50 mL), iced water (90 mL), and potassium phosphate tribasic (20.02 g, 87 mmol). The mixture was stirred for 5 minutes then saturated sodium bicarbonate was added slowly until pH 8. The phases were separated and the aqueous extracted with ethyl acetate (2×50 mL). The combined organic layers were dried over magnesium sulfate and evaporated under reduced pressure. The crude residue was purified via silica gel flash chromatography eluting with 0-30% hexane to ethyl acetate to afford the title compound 5-(difluoromethyl)-5-(3-fluoro-2-methyl-5-nitrophenyl)-2-oxa-4-azabicyclo[4.1.0]hept-3-en-3-amine (0.22 g, 0.698 mmol, 40.1% yield). LC/MS (ESI+) m/z=316.1 (M+H).

Workup

  1. temperature95% (5 mL) and cooled in an ice bath
  2. stirringstirred for 1 hr
  3. stirringThe mixture was stirred for 5 minutes
  4. customThe phases were separated
  5. extractionthe aqueous extracted with ethyl acetate (2×50 mL)
  6. dry with materialThe combined organic layers were dried over magnesium sulfate
  7. customevaporated under reduced pressure
  8. customThe crude residue was purified via silica gel flash chromatography
  9. washeluting with 0-30% hexane to ethyl acetate

Sources & evidence

ORD record
ord-1479c47c3d3241e09d4e1597ec25d443
Source dataset
uspto-grants-2015_07
Patent number
US09085576B2

Reaction notes

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