Ethanol → HCID 70066910, compound

HRID 343326Notes

Reaction equation

HRID 343326 reaction equation
CN(C)C1[C:12]2[C:7](=[CH:8]C=C[C:11]=2[N:13]([CH3:15])C)[CH:6]=CC=1.[Cl:17][C:18]([O:20][CH:21](Cl)[CH3:22])=[O:19].C(O)C>C1(C)C=CC=CC=1>[ClH:17].[CH2:21]([O:20][C:18]([C@H:15]1[CH2:8][C:7]([CH3:6])=[CH:12][CH2:11][NH:13]1)=[O:19])[CH3:22]

Participants

5

Reactant 3

HCID 702EthanolHCID 88675Proton spongeHCID 5213051-Chloroethyl chloroformate

Product 1

HCID 70066910HCID 70066910, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A stirred solution of the above intermediate (13.56 g, 49.7 mmol) in toluene (150 ml), under nitrogen, was heated under reflux for 2 hours, using a Dean-Stark trap. 1,8-Bis(dimethylamino)naphthalene (1.08 g, 5.0 mmol) was then added, heating continued for a further 1 hour, the reaction mixture allowed to cool and the Dean-Stark trap removed. After the addition of 1-chloroethyl chloroformate (10.7 ml, 14.2 g, 99.5 mmol), the reaction mixture was stirred under reflux for 16 hours, allowed to cool, treated with absolute ethanol (80 ml), stirred under reflux for 2 hours more and evaporated under reduced pressure. The residue was partitioned between ethyl acetate (100 ml) and 1M hydrochloric acid (50 ml), then the aqueous phase separated, neutralised with solid sodium bicarbonate and extracted with dichloromethane (3×200 ml). Evaporation under reduced pressure of the dried (MgSO4), combined extracts provided a brown residue which was purified by chromatography on silica gel, using a 0-5% methanol in dichloromethane elution gradient, and then converted to the required hydrochloride salt using excess ethereal hydrogen chloride. The product was further purified by dissolution in dichloromethane (20 ml), filtration (to remove residual silica gel), dilution of the filtrate with ether (200 ml), filtration, washing of the precipitate with ether and drying in vacuo. A sample of this purified product (5.77 g) was crystallised from a mixture of ether and ethanol to afford the title compound as white crystals, m.p. 110°-111° C. Rf 0.35 (SS 3). [α]D25 +113.7° (c=1.0, CH3CH2OH). Found: C,52.79; H,7.94; N,6.68. C9H15NO2 ; HCl requires C,52.55; H,7.84; N,6.81%.

Workup

  1. temperatureunder reflux for 2 hours
  2. temperatureheating
  3. temperatureto cool
  4. customthe Dean-Stark trap removed
  5. temperatureunder reflux for 16 hours
  6. temperatureto cool
  7. stirringstirred
  8. temperatureunder reflux for 2 hours more
  9. customevaporated under reduced pressure
  10. customThe residue was partitioned between ethyl acetate (100 ml) and 1M hydrochloric acid (50 ml)
  11. customthe aqueous phase separated
  12. extractionextracted with dichloromethane (3×200 ml)
  13. customEvaporation under reduced pressure of the
  14. dry with materialdried (MgSO4)
  15. customprovided a brown residue which
  16. customwas purified by chromatography on silica gel
  17. washa 0-5% methanol in dichloromethane elution gradient
  18. customThe product was further purified by dissolution in dichloromethane (20 ml)
  19. filtrationfiltration (to remove residual silica gel), dilution of the filtrate
  20. filtrationwith ether (200 ml), filtration
  21. washwashing of the precipitate with ether
  22. customdrying in vacuo
  23. customA sample of this purified product (5.77 g) was crystallised from a mixture of ether and ethanol

Sources & evidence

ORD record
ord-9bf17a3e852f4c5393c47b7f4bcfb328
Source dataset
uspto-grants-1999_01
Patent number
US05861393

Reaction notes

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