Hydrochloric Acid → Hydrochloric Acid

HRID 1292195Notes

Reaction equation

HRID 1292195 reaction equation
C1(C)C=CC(S(O[CH2:11][C@@H:12]2[O:25][C:16]3=[C:17]4[C:21](=[CH:22][CH:23]=[C:15]3[O:14][CH2:13]2)[NH:20][C:19](=[O:24])[CH2:18]4)(=O)=O)=CC=1.[N-:27]=[N+]=[N-].[Na+].[N-]=[N+]=[N-].[ClH:34]>CN(C=O)C.C(O)C.[Pd]>[NH2:27][CH2:11][CH:12]1[O:25][C:16]2=[C:17]3[C:21](=[CH:22][CH:23]=[C:15]2[O:14][CH2:13]1)[NH:20][C:19](=[O:24])[CH2:18]3.[ClH:34]

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 33557Sodium AzideHCID 33558AzideHCID 15381104(R)-2-(Toluene-4-sulfonyloxymethyl)-2,3,8,9-tetrahydro-7H-1,4-dioxino[2,3-e]indol-8-one

Product 2

HCID 313Hydrochloric AcidHCID 100821902-Aminomethyl-2,3,8,9-tetrahydro-7H-1,4-dioxino[2,3-e]indol-8-one

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
45 °C

Procedure

(R)-2-(Toluene-4-sulfonyloxymethyl)-2,3,8,9-tetrahydro-7H-1,4-dioxino[2,3-e]indol-8-one (3.0 g, 8.0 mmole) and sodium azide (1.6 g, 24.0 mmole) were placed in 300 ml of DMF and the reaction mixture was heated at 45° C. for 15 hours. Most of the DMF was removed and the residue was partitioned between dichloromethane and water. The dichloromethane layer was separated, dried over anhydrous magnesium sulfate and concentrated. The residue was pure enough without further purification and was identified as the desired product, (S)-2-azidomethyl-2,3,8,9-tetrahydro-7H-1,4-dioxino[2,3-e]indol-8-one. An aliquot amount of the azide (0.8 g, 3.2 mmole) in ethanol (50 ml) was hydrogenated with 10% palladium on carbon (100 mg) for 15 hours. The resulting mixture was acidified with 4N isopropanolic HCl until pH<3. The catalyst was then filtered off and the filtrate was concentrated. The residue was dissolved in 90% aqueous ethanol and precipitated with diethyl ether to give the (S) enantiomer of the title compound as a white solid hydrochloride, 1.25 hydrate, (0.7 g, 85%), m.p. 278°-280° C.

Workup

  1. customMost of the DMF was removed
  2. customthe residue was partitioned between dichloromethane and water
  3. customThe dichloromethane layer was separated
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated
  6. customThe residue was pure enough without further purification
  7. filtrationThe catalyst was then filtered off
  8. concentrationthe filtrate was concentrated
  9. dissolutionThe residue was dissolved in 90% aqueous ethanol
  10. customprecipitated with diethyl ether

Sources & evidence

ORD record
ord-ec10fc8499264b32b07738d68c416604
Source dataset
uspto-grants-1998_05
Patent number
US05756532

Reaction notes

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