Nitric Acid → HCID 71112643, compound

HRID 876379Notes

Reaction equation

HRID 876379 reaction equation
[F:1][C:2]1([F:18])[CH2:7][O:6][C:5]([NH2:8])=[N:4][C@:3]1([CH2:16][F:17])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[F:15].S(=O)(=O)(O)O.[N+:24]([O-])([OH:26])=[O:25].[OH-].[Na+]>O>[F:18][C:2]1([F:1])[CH2:7][O:6][C:5]([NH2:8])=[N:4][C@:3]1([CH2:16][F:17])[C:9]1[CH:14]=[C:13]([N+:24]([O-:26])=[O:25])[CH:12]=[CH:11][C:10]=1[F:15]

Participants

6

Reactant 4

HCID 944Nitric AcidHCID 1118Sulfuric AcidHCID 14798Sodium HydroxideHCID 86712810HCID 86712810, compound

Product 1

HCID 71112643HCID 71112643, compoundYield 102.4%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A dispersion of (S)-5,5-difluoro-4-fluoromethyl-4-(2-fluoro-phenyl)-5,6-dihydro-4H-[1,3]oxazin-2-ylamine (intermediate F6.1) (32.5 mg, 124 μmol) in sulfuric acid (1.01 g, 554 μl, 9.92 mmol) was cooled to 0° C. and stirring was continued until a complete solution was obtained. At 0° C. fuming nitric acid (12.1 mg, 8.68 μl, 174 μmol) was added in one portion and stifling continued for 2 hours. For the workup, the solution was added dropwise to a mixture of crushed ice and water. With an aqueous solution of sodium hydroxide (6 M) the pH was adjusted to 7-8. The aqueous layer was extracted three times with ethyl acetate, thereafter the combined organic layers were washed with brine, then dried over sodium sulphate and evaporated at reduced pressure. The (S)-5,5-difluoro-4-fluoromethyl-4-(2-fluoro-5-nitro-phenyl)-5,6-dihydro-4H-[1,3]oxazin-2-ylamine (39 mg, quantitative yield) was obtained as a light yellow solid and was engaged in the following step without further purification. MS (ISP): m/z=308.3 [M+H]+.

Workup

  1. customwas obtained
  2. extractionThe aqueous layer was extracted three times with ethyl acetate
  3. washthe combined organic layers were washed with brine
  4. dry with materialdried over sodium sulphate
  5. customevaporated at reduced pressure

Sources & evidence

ORD record
ord-88d9ec37ff5c451eafe70f6999db7440
Source dataset
uspto-grants-2015_03
Patent number
US08987255B2

Reaction notes

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