Ammonium formate → HCID 67045347, compound

HRID 2367120Notes

Reaction equation

HRID 2367120 reaction equation
[N:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2([OH:28])[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:12](=[O:19])[N:11]2[C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([Cl:26])[C:21]=2[F:27])=[CH:6][C:5]=1[N+:29]([O-])=O)=[N+]=[N-].O1CCCC1.O.C([O-])=O.[NH4+]>C(OCC)(=O)C.[Fe]>[Cl:26][C:22]1[C:21]([F:27])=[C:20]([N:11]2[C:10]([C:7]3[CH:8]=[CH:9][C:4]([NH2:1])=[C:5]([NH2:29])[CH:6]=3)([OH:28])[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:12]2=[O:19])[CH:25]=[CH:24][CH:23]=1

Participants

6

Reactant 3

HCID 2723923Ammonium formateHCID 21881883Oxolane--water (1/1)HCID 86617514HCID 86617514, compound

Product 1

HCID 67045347HCID 67045347, compoundYield 56%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-(4-azido-3-nitrophenyl)-2-(3-chloro-2-fluorophenyl)-3-hydroxy-2,3-dihydro-1H-isoindol-1-one (7.0 g, 16.00 mmol) in a mixture tetrahydrofurane-water (1:1, 15.0 ml) ammonium formate (5.0 g, 79.30 mmol), was added followed by the addition of iron (4.0 g, 71.60 mmol). The reaction mixture was heated to reflux and stirred for 320 minutes. It was cooled to room temperature and diluted with ethyl acetate (70 mL). The resulting slurry was filtered through a pad of Celite and washed with ethyl acetate (3×30 mL). It was partitioned with water and the organic layer was washed with water (30 mL), brine (30 mL) and dried over anhydrous sodium sulfate. Filtration and concentration resulted in a yellow oily product. It was crystallized from diethyl ether by the addition of hexane. The product was collected by filtration, dried in vacuo, to provide 2-(3-chloro-2-fluorophenyl)-3-(3,4-diaminophenyl)-3-hydroxy-2,3-dihydro-1H-isoindol-1-one (3.42 g, 56% yield). 1H NMR (400 MHz, CD3OD): 7.85 (d, J=7.6 Hz, 1H), 7.65-7.58 (m, 2H), 7.41-7.34 (m, 2H), 7.17 (t, J=6.4 Hz. 1H), 7.05 (t, J=8 Hz, 1H), 6.69 (s, 1H), 6.57 (s, 2H); MS (EI) for C20H15ClFN3O2: 382 (M−).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux
  3. filtrationThe resulting slurry was filtered through a pad of Celite
  4. washwashed with ethyl acetate (3×30 mL)
  5. customIt was partitioned with water
  6. washthe organic layer was washed with water (30 mL), brine (30 mL)
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationFiltration and concentration
  9. customresulted in a yellow oily product
  10. customIt was crystallized from diethyl ether by the addition of hexane
  11. filtrationThe product was collected by filtration
  12. customdried in vacuo

Sources & evidence

ORD record
ord-30fbb99cc668462f8bccbd56adc8fee7
Source dataset
uspto-grants-2014_04
Patent number
US08697737B2

Reaction notes

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