Methanol → 3-(5-Methoxy-benzo[b]thiophen-2-yl)-8-aza-bicyclo[3.2.1]oct-2-ene hydrochloric acid salt

HRID 472774Notes

Reaction equation

HRID 472774 reaction equation
[CH3:1][O:2][C:3]1[CH:20]=[CH:19][C:6]2[S:7][C:8]([C:10]3[CH2:16][CH:15]4[N:17](C)[CH:12]([CH2:13][CH2:14]4)[CH:11]=3)=[CH:9][C:5]=2[CH:4]=1.[Cl:21]C(OC(Cl)=O)C.CO>C1(C)C=CC=CC=1>[ClH:21].[CH3:1][O:2][C:3]1[CH:20]=[CH:19][C:6]2[S:7][C:8]([C:10]3[CH2:16][CH:15]4[NH:17][CH:12]([CH2:13][CH2:14]4)[CH:11]=3)=[CH:9][C:5]=2[CH:4]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 5213051-Chloroethyl chloroformateHCID 674009753-(5-Methoxy-benzo[b]thiophen-2-yl)-8-methyl-8-aza-bicyclo[3.2.1]oct-2-ene

Product 1

HCID 674487573-(5-Methoxy-benzo[b]thiophen-2-yl)-8-aza-bicyclo[3.2.1]oct-2-ene hydrochloric acid salt

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

3-(5-Methoxy-benzo[b]thiophen-2-yl)-8-methyl-8-aza-bicyclo[3.2.1]oct-2-ene (2.28 g, 7.99 mmol) was solved in toluene (25 ml). 1-Chloroethylchloroformate (2.28 g, 15.97 mmol) was added at room-temperature. The mixture was stirred at room-temperature for 1 hour and was then stirred at reflux for 15 hours. Methanol (20 ml) was added followed by reflux for 2 hours. The mixture was cooled on an ice-bath. The product crystallized and was washed with ethanol and diethylether. The product was recrystallised from ethanol as hydrochloric acid salt, yield 0.37 g (15%). The mother liquor was evaporated, converted to the free base by adding aqueous ammonia and extraction with dichloromethane followed by chromatographic purification using dichloromethane, methanol and aqueous ammonia (9:1+1%). Yield 0.30 g (14%).

Workup

  1. stirringwas then stirred
  2. temperatureat reflux for 15 hours
  3. temperatureby reflux for 2 hours
  4. temperatureThe mixture was cooled on an ice-bath
  5. customThe product crystallized
  6. washwas washed with ethanol and diethylether
  7. customThe product was recrystallised from ethanol as hydrochloric acid salt, yield 0.37 g (15%)
  8. customThe mother liquor was evaporated
  9. additionby adding aqueous
  10. extractionammonia and extraction with dichloromethane
  11. customfollowed by chromatographic purification

Sources & evidence

ORD record
ord-280c62eb51c44c9eb61f0c2a8c738a1a
Source dataset
uspto-grants-2014_01
Patent number
US08633218B2

Reaction notes

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