Methyl 2-(3-((benzylamino)methyl)-6-nitro-2,3-dihydrobenzo[b][1,4]dioxin-5-yl)acetate → 2-((Benzylamino)methyl)-2,3-dihydro-7H-[1,4]dioxino[2,3-e]indol-8(9H)-one

HRID 1444808Notes

Reaction equation

HRID 1444808 reaction equation
[CH2:1]([NH:8][CH2:9][CH:10]1[CH2:15][O:14][C:13]2[CH:16]=[CH:17][C:18]([N+:25]([O-])=O)=[C:19]([CH2:20][C:21](OC)=[O:22])[C:12]=2[O:11]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>C(OCC)(=O)C.C(O)C>[CH2:1]([NH:8][CH2:9][CH:10]1[O:11][C:12]2=[C:19]3[C:18](=[CH:17][CH:16]=[C:13]2[O:14][CH2:15]1)[NH:25][C:21](=[O:22])[CH2:20]3)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

3

Reactant 1

HCID 59168987Methyl 2-(3-((benzylamino)methyl)-6-nitro-2,3-dihydrobenzo[b][1,4]dioxin-5-yl)acetate

Product 1

HCID 99103252-((Benzylamino)methyl)-2,3-dihydro-7H-[1,4]dioxino[2,3-e]indol-8(9H)-oneYield 22%

Reagents, catalysts & solvents 1

HCID 21584252Ethanol ethylacetateSolvent

Conditions

Temperature
70 °C

Procedure

The methyl ester from Example 5 (43 mg) was dissolved in 1:1 ethyl acetate/ethanol (10 mL) and filtered through a syringe filter to remove insoluble material. Platinum oxide (35 weight percent) was added and the mixture placed under 50 psi of hydrogen gas on a Parr shaker overnight. TLC analysis with 95:5 CH2Cl2/MeOH showed consumption of starting material with a more polar product having been formed. The mixture was filtered through a 0.5 μm syringe filter, washing with 1:1 EtOAc/EtOH, and the filtrate concentrated under reduced pressure to a pale red-brown glass. The crude material was redissolved in ethanol (20 mL) and 20 μL of concentrated HCl were added. The solution was warmed to 70° C. and allowed to stir overnight. TLC of the reaction mixture (96:4 CH2Cl2/MeOH) showed the formation of a new product with no remaining starting material. The reaction mixture was cooled to ambient temperature and concentrated under reduced pressure to a light orange film. This was chromatographed over silica gel eluting with 96:4 CH2Cl2/MeOH. The title product was isolated in 22% yield.

Workup

  1. filtrationfiltered through a syringe
  2. filtrationfilter
  3. customto remove insoluble material
  4. additionPlatinum oxide (35 weight percent) was added
  5. customplaced under 50 psi of hydrogen gas on a Parr shaker overnight
  6. customconsumption of starting material with a more polar product
  7. customhaving been formed
  8. filtrationThe mixture was filtered through a 0.5 μm syringe
  9. filtrationfilter
  10. washwashing with 1:1 EtOAc/EtOH
  11. concentrationthe filtrate concentrated under reduced pressure to a pale red-brown glass
  12. dissolutionThe crude material was redissolved in ethanol (20 mL)
  13. addition20 μL of concentrated HCl were added
  14. temperatureThe reaction mixture was cooled to ambient temperature
  15. concentrationconcentrated under reduced pressure to a light orange film
  16. customThis was chromatographed over silica gel eluting with 96:4 CH2Cl2/MeOH

Sources & evidence

ORD record
ord-e667eaf7c64f4aeab5c63a5b248a8d38
Source dataset
uspto-grants-2010_02
Patent number
US07662979B2

Reaction notes

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