Benzylamine → HCID 70417949, compound

HRID 2231293Notes

Reaction equation

HRID 2231293 reaction equation
[CH2:1]([C@:3]1([CH:21]([CH3:25])[C:22](O)=[O:23])[C@@H:12]2[N:7]([CH2:8][CH2:9][C:10]3[C:19]4[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=4)[N:13]([CH3:20])[C:11]=32)[CH2:6][CH2:5][CH2:4]1)[CH3:2].CN1CCOCC1.ClC(OCC)=O.[CH2:39]([NH2:46])[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1>O1CCCC1>[CH2:39]([NH:46][C:22](=[O:23])[CH:21]([C@@:3]1([CH2:4][CH3:5])[C@@H:12]2[N:7]([CH2:8][CH2:9][C:10]3[C:19]4[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=4)[N:13]([CH3:20])[C:11]=32)[CH2:6][CH2:2][CH2:1]1)[CH3:25])[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1

Participants

6

Reactant 4

HCID 7504BenzylamineHCID 79724-MethylmorpholineHCID 10928Ethyl chloroformateHCID 70417581HCID 70417581, compound

Product 1

HCID 70417949HCID 70417949, compoundYield 78%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-5 °C

Procedure

3.40 g. (0.01 moles) of (-)-(1S,12bS)-1-ethyl-12-methyl-1,2,3,4,6,7,12,12b-octahydroindolo[2,3-a]quinolizin-1-yl-propionic acid are added to a solution containing 2.04 g. (0.02 moles) of N-methylmorpholine (redistilled from sodium) in 20 ml. of dry tetrahydrofuran while stirring under nitrogen, then the solution is cooled to -5° C. and 1.10 g. (0.01 mole) of ethyl chloroformate are rapidly dropped in while stirring vigorously and keeping the inner temperature at or lower than 0° C. The mixture is stirred at 0° C. for 30 minutes, whereupon a solution containing 1.18 g. (0.011 moles) of benzylamine in 10 ml. of dry tetrahydrofuran is dropwise added at a temperature between -5° C. and 0° C. during 10 minutes. The mixture is stirred at 0° C. for 30 minutes, then during an additional stirring for 4 hours the mixture is allowed to warm to room temperature. The mixture is evaporated on a rotating evaporator and after shaking thoroughly the residue with 50 ml. of dichloromethane and 20 ml. of water, the phases are separated. The dichloromethane layer is washed at first with 20 ml. of 5% sodium carbonate solution, then three times with 20 ml. of water each, dried over anhydrous magnesium sulphate and evaporated. The residue which is the crude product, is purified by column chromatography on silica gel by using toluene containing 10% of diethylamine to give 3.36 g. (78% yield) of the title compound as an oily product.

Workup

  1. additioncontaining 2.04 g
  2. customlower than 0° C
  3. stirringThe mixture is stirred at 0° C. for 30 minutes, whereupon a solution
  4. additioncontaining 1.18 g
  5. stirringThe mixture is stirred at 0° C. for 30 minutes
  6. stirringduring an additional stirring for 4 hours the mixture
  7. temperatureto warm to room temperature
  8. customThe mixture is evaporated on a rotating evaporator
  9. stirringafter shaking thoroughly the residue with 50 ml
  10. customof water, the phases are separated
  11. washThe dichloromethane layer is washed at first with 20 ml
  12. dry with materialof water each, dried over anhydrous magnesium sulphate
  13. customevaporated
  14. customis purified by column chromatography on silica gel
  15. customto give 3.36 g

Sources & evidence

ORD record
ord-175a9c96620847e8be0d08b921f54729
Source dataset
uspto-grants-1988_11
Patent number
US04782052

Reaction notes

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