Sulfuric Acid → HCID 86715908, compound

HRID 627640Notes

Reaction equation

HRID 627640 reaction equation
[NH2:1][C:2]1[C:7]([CH3:9])([CH3:8])[S:6](=[O:11])(=[O:10])[CH2:5][C@@:4]([CH2:19][F:20])([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[F:18])[N:3]=1.S(=O)(=O)(O)O.[N+:26]([O-])([O-:28])=[O:27].[K+].[OH-].[NH4+]>O>[NH2:1][C:2]1[C:7]([CH3:9])([CH3:8])[S:6](=[O:11])(=[O:10])[CH2:5][C@:4]([C:12]2[CH:17]=[C:16]([N+:26]([O-:28])=[O:27])[CH:15]=[CH:14][C:13]=2[F:18])([CH2:19][F:20])[N:3]=1

Participants

6

Reactant 4

HCID 1118Sulfuric AcidHCID 14923Ammonium HydroxideHCID 24434Potassium NitrateHCID 86728108HCID 86728108, compound

Product 1

HCID 86715908HCID 86715908, compoundYield 101.4%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a solution of (S)-5-amino-3-(fluoromethyl)-3-(2-fluorophenyl)-6,6-dimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide (1.98 g, 6.55 mmol) in sulfuric acid (8.73 mL, 0.16 mol) at 0° C. was added potassium nitrate (0.69 g, 6.88 mmol) portion wise. When the addition was completed, the reaction mixture was allowed to warm to room temperature and the mixture was stirred at room temperature for 30 min. The reaction mixture was carefully poured over ice-water (100 mL) and neutralized by the addition of aqueous ammonium hydroxide. The mixture was diluted with water (10 mL) and extracted with ethyl acetate (2×50 mL). The combined organic extracts were washed with brine, dried over sodium sulfate, filtered, and concentrated under vacuum to give the title compound (2.27 g, 6.64 mmol) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ 8.43 (dd, J=3.03, 6.75 Hz, 1H), 8.25 (td, J=3.55, 8.95 Hz, 1H), 7.51 (dd, J=9.00, 11.35 Hz, 1H), 6.58 (br. s., 2H), 4.59 (q, J=8.80 Hz, 1H), 4.48 (q, J=8.80 Hz, 1H), 3.68-3.87 (m, 2H), 1.61 (s, 3H), 1.47 (s, 3H). LC/MS (ESI+) m/z=348 (M+H).

Workup

  1. additionWhen the addition
  2. extractionextracted with ethyl acetate (2×50 mL)
  3. washThe combined organic extracts were washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-cbe4b1abdb594c25a640d32f8540f28f
Source dataset
uspto-grants-2016_04
Patent number
US09309263B2

Reaction notes

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