Hydrogen Peroxide → HCID 86732146, compound

HRID 930317Notes

Reaction equation

HRID 930317 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5](B2OC(C)(C)C(C)(C)O2)=[CH:4][C:3]=1[C@:17]1([CH2:36][F:37])[CH2:22][C@@H:21]([C:23]([F:26])([F:25])[F:24])[O:20][C:19]([NH:27][C:28](=[O:35])[C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)=[N:18]1.OO.O.C([O-])(O)=[O:42].[Na+]>C1COCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([OH:42])=[CH:4][C:3]=1[C@:17]1([CH2:36][F:37])[CH2:22][C@@H:21]([C:23]([F:24])([F:25])[F:26])[O:20][C:19]([NH:27][C:28](=[O:35])[C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)=[N:18]1

Participants

6

Reactant 4

HCID 784Hydrogen PeroxideHCID 962WaterHCID 516892Sodium BicarbonateHCID 86732144HCID 86732144, compound

Product 1

HCID 86732146HCID 86732146, compoundYield 56%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of N-((4S,6S)-4-(2-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-yl)benzamide (4.16 g, 7.93 mmol) in THF (22.67 mL) at 0° C. was added hydrogen peroxide 30% in water (2.431 mL, 23.80 mmol). The reaction mixture was stirred at 0° C. to room temperature for 16 h. The reaction mixture was acidified to pH 5-7 by addition of saturated NaHCO3, and extracted with EtOAc (2×). The combined organics were washed with water and brine, dried and concentrated. The crude material was purified by chromatography through a Redi-Sep pre-packed silica gel column (40 g), eluting with a gradient of 0-30% EtOAc in hexane, to provide N-((4S,6S)-4-(2-fluoro-5-hydroxyphenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-yl)benzamide (1.84 g, 4.44 mmol, 56.0% yield) as white foam. MS m/z=415 [M]+. Calculated for C19H15F5N2O3: 414.33.

Workup

  1. extractionextracted with EtOAc (2×)
  2. washThe combined organics were washed with water and brine
  3. customdried
  4. concentrationconcentrated
  5. customThe crude material was purified by chromatography through a Redi-Sep pre-packed silica gel column (40 g)
  6. washeluting with a gradient of 0-30% EtOAc in hexane

Sources & evidence

ORD record
ord-4642887ca10d43c59297f241271e0186
Source dataset
uspto-grants-2016_03
Patent number
US09296734B2

Reaction notes

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