Benzylamine → HCID 70418373, compound

HRID 2231291Notes

Reaction equation

HRID 2231291 reaction equation
[CH2:1]([C@:3]1([CH2:20][C:21](O)=[O:22])[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)[NH:13][C:11]=32)[CH2:6][CH2:5][CH2:4]1)[CH3:2].CN1CCOCC1.ClC(OCC)=O.[CH2:37]([NH2:44])[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1>O1CCCC1.C1C=CC=CC=1>[CH2:37]([NH:44][C:21](=[O:22])[CH2:20][C@@:3]1([CH2:1][CH3:2])[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)[NH:13][C:11]=32)[CH2:6][CH2:5][CH2:4]1)[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1

Participants

7

Reactant 4

HCID 7504BenzylamineHCID 79724-MethylmorpholineHCID 10928Ethyl chloroformateHCID 15116173HCID 15116173, compound

Product 1

HCID 70418373HCID 70418373, compoundYield 44%

Reagents, catalysts & solvents 2

HCID 241BenzeneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-5 °C

Procedure

3.12 g. (0.01 mole) of (-)-(1S,12bS)-1-ethyl-1,2,3,4,6,7,12,12b-octahydro-indol[2,3-a]quinolizin-1-yl-acetic 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, then a mixture 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 and then during an additional stirring for 4 hours the temperature of the mixture is allowed to warm to room temperature. The mixture is evaporated on a rotating evaporator. After shaking thoroughly the residue with 50 ml. of dichloromethane and 20 ml. of water, the phases are separated. The dichloromethane solution is washed with 20 ml. of 5% sodium carbonate solution and 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 as eluant to give 1.89 g. (44% yield) of the title product which can further be purified by recrystallization from benzene, m.p. 179°-180° C.

Workup

  1. additioncontaining 2.04 g
  2. customlower than 0° C
  3. stirringThe mixture is stirred at 0° C. for 30 minutes
  4. additiona mixture containing 1.18 g
  5. stirringThe mixture is stirred at 0° C. for 30 minutes
  6. stirringduring an additional stirring for 4 hours the temperature of 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 solution is washed with 20 ml
  12. dry with materialof 5% sodium carbonate solution and then three times with 20 ml of water each, dried over anhydrous magnesium sulphate
  13. customevaporated
  14. customis purified by column chromatography on silica gel
  15. customto give 1.89 g

Sources & evidence

ORD record
ord-7df8a05458904c79a30940471585376e
Source dataset
uspto-grants-1988_11
Patent number
US04782052

Reaction notes

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