Sodium Hydroxide → (4S,6S)-4-(2-fluoro-3-methyl-5-nitrophenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine

HRID 930422Notes

Reaction equation

HRID 930422 reaction equation
[F:1][C:2]1[C:7]([CH3:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C@:9]1([CH2:20][F:21])[CH2:14][C@@H:13]([C:15]([F:18])([F:17])[F:16])[O:12][C:11]([NH2:19])=[N:10]1.[N+:22]([O-])([O-:24])=[O:23].[K+].[O-]P([O-])([O-])=O.[K+].[K+].[K+].C([O-])(O)=O.[Na+].[OH-].[Na+]>OS(O)(=O)=O.O.C(Cl)Cl>[F:1][C:2]1[C:7]([CH3:8])=[CH:6][C:5]([N+:22]([O-:24])=[O:23])=[CH:4][C:3]=1[C@:9]1([CH2:20][F:21])[CH2:14][C@@H:13]([C:15]([F:17])([F:18])[F:16])[O:12][C:11]([NH2:19])=[N:10]1

Participants

9

Reactant 5

HCID 14798Sodium HydroxideHCID 24434Potassium NitrateHCID 62657Potassium Phosphate, TribasicHCID 516892Sodium BicarbonateHCID 86732260(4S,6S)-4-(2-fluoro-3-methylphenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine

Product 1

HCID 86732262(4S,6S)-4-(2-fluoro-3-methyl-5-nitrophenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amineYield 97.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1118Sulfuric AcidSolventHCID 6344DichloromethaneSolvent

Procedure

(4S,6S)-4-(2-fluoro-3-methylphenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine (1.13 g, 3.67 mmol) was dissolved in conc. H2SO4 (20 mL) and cooled in an ice-bath. Then potassium nitrate (0.264 ml, 5.50 mmol) was added in one portion and the reaction was stirred for 5 min, removed from the ice-bath and after 5 min at room temperature LCMS showed the reaction went to completion and ice was added. The reaction mixture was poured into a mixture of DCM, water, ice and potassium phosphate tribasic (61.5 g, 290 mmol) and stirred for 5 min followed by the slowly addition of saturated NaHCO3. The mixture was neutralized with 5 N NaOH and extracted with DCM. The combined organics were dried over Na2SO4, filtered and concentrated to afford a pale yellow foam as (4S,6S)-4-(2-fluoro-3-methyl-5-nitrophenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine (1.26 g, 3.57 mmol, 97% yield). MS m/z=353.9 [M+H]+. Calculated for C13H12F5N3O3: 353.08.

Workup

  1. temperaturecooled in an ice-bath
  2. customremoved from the ice-bath and after 5 min at room temperature LCMS
  3. additionwas added
  4. stirringstirred for 5 min
  5. extractionextracted with DCM
  6. dry with materialThe combined organics were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-59310aadad2d4eec8c8bd6349901bec4
Source dataset
uspto-grants-2016_03
Patent number
US09296734B2

Reaction notes

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