Nitric Acid → HCID 70654349, compound

HRID 2178204Notes

Reaction equation

HRID 2178204 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C@:8]1([CH3:21])[C@@H:17]2[C@H:13]([CH2:14][O:15][CH2:16]2)[S:12](=[O:19])(=[O:18])[CH2:11][C:10]([NH2:20])=[N:9]1.FC(F)(F)C(O)=O.S(=O)(=O)(O)O.[N+:34]([O-])([OH:36])=[O:35].[OH-].[Na+]>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N+:34]([O-:36])=[O:35])=[CH:4][C:3]=1[C@:8]1([CH3:21])[C@@H:17]2[C@H:13]([CH2:14][O:15][CH2:16]2)[S:12](=[O:18])(=[O:19])[CH2:11][C:10]([NH2:20])=[N:9]1

Participants

6

Reactant 5

HCID 944Nitric Acid2×HCID 1118Sulfuric AcidHCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 70654458HCID 70654458, compound

Product 1

HCID 70654349HCID 70654349, compound

Conditions

Temperature
0 °C

Procedure

A solution of (3aR,8S,8aS)-rel-8-(2-fluoro-phenyl)-8-methyl-4,4-dioxo-3,3a,4,5,8,8a-hexahydro-1H-2-oxa-4λ6-thia-7-aza-azulen-6-ylamine (110 mg, 176 μmol) in trifluoroacetic acid (1.33 g, 11.7 mmol) was cooled to 0-5° C. Sulfuric acid (149 mg, 81.2 μl, 1.52 mmol), then nitric acid (12.1 mg, 8.01 μl, 192 μmol) was added slowly. The reaction mixture was stirred at 0° C. for 1 hour. In order to complete the reaction, another equivalent of nitric acid (12.1 mg, 8.01 μl, 192 μmol) was added and stirring continued at 0° C. for 2 hours. For the workup, ice-water was added to the reaction mixture, and the resulting suspension was set to pH ˜12 by addition of a solution of sodium hydroxide (32%). The mixture was extracted twice with ethyl acetate. The combined organic layers were washed with water, dried over sodium sulphate and evaporated. The crude (3aR,8S,8aS)-rel-8-(2-fluoro-5-nitro-phenyl)-8-methyl-4,4-dioxo-3,3a,4,5,8,8a-hexahydro-1H-2-oxa-4λ6-thia-7-aza-azulen-6-ylamine was obtained as a brown solid and was engaged in the next step without purification. MS (ISP): m/z=358.3 [M+H]+.

Workup

  1. customthe reaction
  2. stirringstirring
  3. waitcontinued at 0° C. for 2 hours
  4. extractionThe mixture was extracted twice with ethyl acetate
  5. washThe combined organic layers were washed with water
  6. dry with materialdried over sodium sulphate
  7. customevaporated

Sources & evidence

ORD record
ord-a92bf6a0b35d43039a963fc3202508bd
Source dataset
uspto-grants-2015_06
Patent number
US09067924B2

Reaction notes

Loading…