Hydrochloric Acid → Norchlorcyclizine

HRID 1803050Notes

Reaction equation

HRID 1803050 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[N:9]2[CH2:14][CH2:13][N:12](CC3C=CC(OC)=CC=3)[CH2:11][CH2:10]2)=[CH:4][CH:3]=1.ClC(OC(Cl)C)=O.Cl>O1CCCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]([C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)[N:9]2[CH2:10][CH2:11][NH:12][CH2:13][CH2:14]2)=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 5213051-Chloroethyl chloroformateHCID 67080122HCID 67080122, compound

Product 1

HCID 9340NorchlorcyclizineYield 63.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
27.5 °C

Procedure

35 ml tetrahydrofuran was added to 10 gms (0.02463 moles) of compound obtained from Example 3 followed by slow addition of 4 gms (0.02797 moles) 1-chloroethyl chloroformate in 10 ml of tetrahydrofuran. The reaction mass was heated at reflux temperature for about 3 hours and concentrated to an oil. To the oil 50 ml of methanol was added, heated to reflux for about 16 hours and concentrated to get a residue. The residue was further treated with 50 ml of aqueous HCl and washed with dichloromethane (3×30 ml). To the aqueous layer 2 ml of n-Heptane was added and then treated with sodium hydroxide solution at 25-30° C. The reaction mass was stirred at 25-30° C. for about 12 hours. After completion of the reaction the product obtained was filtered and dried under vacuum at 50-55° C. to obtain the title compound (4.5 gms).

Workup

  1. temperatureThe reaction mass was heated
  2. temperatureat reflux temperature for about 3 hours
  3. concentrationconcentrated to an oil
  4. additionTo the oil 50 ml of methanol was added
  5. temperatureheated
  6. temperatureto reflux for about 16 hours
  7. concentrationconcentrated
  8. customto get a residue
  9. washwashed with dichloromethane (3×30 ml)
  10. additionTo the aqueous layer 2 ml of n-Heptane was added
  11. additiontreated with sodium hydroxide solution at 25-30° C
  12. customAfter completion of the reaction the product
  13. customobtained
  14. filtrationwas filtered
  15. customdried under vacuum at 50-55° C.

Sources & evidence

ORD record
ord-a0a7b6f40859461d831fa6fc3a86b3ab
Source dataset
uspto-grants-2013_01
Patent number
US08350031B2

Reaction notes

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