Trifluoroacetic anhydride → HCID 67263916, compound

HRID 1041640Notes

Reaction equation

HRID 1041640 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]2[O:11][CH2:10][CH2:9][NH:8][C:7](=[O:12])[C:6]=2[CH:13]=1.FC(F)(F)C(OC(=O)C(F)(F)F)=O.[N+:27]([O-])([O-:29])=[O:28].[K+].[OH-].[Na+]>C(#N)C>[F:1][C:2]1[CH:3]=[C:4]([N+:27]([O-:29])=[O:28])[C:5]2[O:11][CH2:10][CH2:9][NH:8][C:7](=[O:12])[C:6]=2[CH:13]=1

Participants

6

Reactant 4

HCID 9845Trifluoroacetic anhydrideHCID 14798Sodium HydroxideHCID 24434Potassium NitrateHCID 552506527-Fluoro-3,4-dihydro-1,4-benzoxazepin-5(2H)-one

Product 1

HCID 67263916HCID 67263916, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

7-Fluoro-3,4-dihydro-2H-benzo[f][1,4]oxazepin-5-one (346 mg, 1.91 mmol) in Acetonitrile (10 mL) and Trifluoroacetic anhydride (0.85 mL, 6.0 mmol) was treated with Potassium nitrate (0.203 g, 2.00 mmol) at room temperature for 24 h. Aq. NaOH (15% w/w, 10 mL) was added and the mixture extracted 3×15 mL DCM. The DCM extract was washed with water (20 mL) and brine (20 mL) then dried over sodium sulfate and conc. in vacuo. 1H-, 19F-NMR and HPLC showed a 2-3:1 mixture of 7-Fluoro-9-nitro-3,4-dihydro-2H-benzo[f][1,4]oxazepin-5-one and 7-Fluoro-3,4-dihydro-2H-benzo[f][1,4]oxazepin-5-one, which was chromatographed (ISCO, 40 g, 0-75% EtOAc:Hex) to give 7-Fluoro-9-nitro-3,4-dihydro-2H-benzo[f][1,4]oxazepin-5-one, enriched in the mixture, but still containing 7-Fluoro-3,4-dihydro-2H-benzo[f][1,4]oxazepin-5-one. This mixture was dissolved in Ethanol (10 mL) and added to Palladium on Carbon 10% (0.05 g) wetted with a small amount of water. The mixture was shaken under an atmosphere of Hydrogen (40 psi) for 1.5 h, then filtered through Celite, washing with ethanol. Conc. in vacuo gave a white solid, which was taken up in Et2O with minimal MeOH to solubilize, then extracted with 15 mL 1N HCl. The aq. extract was washed once with ether (10 mL) then basified with 15% NaOH, then extracted 8×10 mL DCM. The organic layers were dried over sodium sulfate and conc. in vacuo to give 9-Amino-7-fluoro-3,4-dihydro-2H-benzo[f][1,4]oxazepin-5-one as a white solid (120 mg, 35% over two steps.

Workup

  1. extractionthe mixture extracted 3×15 mL DCM
  2. extractionThe DCM extract
  3. washwas washed with water (20 mL) and brine (20 mL)
  4. dry with materialthen dried over sodium sulfate and conc. in vacuo
  5. additiona 2-3:1 mixture of 7-Fluoro-9-nitro-3,4-dihydro-2H-benzo[f][1,4]oxazepin-5-one and 7-Fluoro-3,4-dihydro-2H-benzo[f][1,4]oxazepin-5-one, which
  6. customwas chromatographed (ISCO, 40 g, 0-75% EtOAc:Hex)

Sources & evidence

ORD record
ord-1f9b762e06804772a5fedb71df657d1a
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

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