Sulfuric Acid → HCID 86732227, compound

HRID 930394Notes

Reaction equation

HRID 930394 reaction equation
[F:1][C:2]1[C:7]([F: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.S(=O)(=O)(O)O.[N+:27]([O-])([O-:29])=[O:28].[Na+]>>[F:1][C:2]1[C:7]([F:8])=[CH:6][C:5]([N+:27]([O-:29])=[O:28])=[CH:4][C:3]=1[C@:9]1([CH2:20][F:21])[CH2:14][C@@H:13]([C:15]([F:16])([F:17])[F:18])[O:12][C:11]([NH2:19])=[N:10]1

Participants

4

Reactant 3

HCID 1118Sulfuric AcidHCID 24268Sodium NitrateHCID 86732225HCID 86732225, compound

Product 1

HCID 86732227HCID 86732227, compound

Procedure

To a cooled (ice bath) solution of (4S,6S)-4-(2,3-difluorophenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine (1.62 g, 5.19 mmol) in sulfuric acid (24 mL, 450 mmol) was added sodium nitrate (0.573 g, 6.75 mmol) in one portion. After stirred for 15 min, The ice bath was removed and the mixture was stirred for 3 h at room temperature. Reaction was cooled with ice bath, quenched with ice water and basified by addition of potassium carbonate (50 g) in small portion. The resulted suspension was extracted with EtOAc (2×). The organic extracts were washed with brine, dried over Na2SO4 and filtered. The filtrate was concentrated and dried in vacuum to afford crude (4S,6S)-4-(2,3-difluoro-5-nitrophenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine as yellow oil. It was carried to next step without purification. Assume theoretical yield. MS m/z=358.1 [M+H]+. Calculated for C12H9F6N3O3: 357.2

Workup

  1. customThe ice bath was removed
  2. stirringthe mixture was stirred for 3 h at room temperature
  3. customReaction
  4. temperaturewas cooled with ice bath
  5. customquenched with ice water
  6. additionbasified by addition of potassium carbonate (50 g) in small portion
  7. extractionThe resulted suspension was extracted with EtOAc (2×)
  8. washThe organic extracts were washed with brine
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. concentrationThe filtrate was concentrated
  12. customdried in vacuum

Sources & evidence

ORD record
ord-4f5972f3f16b4459b6115a154a76a3e0
Source dataset
uspto-grants-2016_03
Patent number
US09296734B2

Reaction notes

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