4-Methylmorpholine → HCID 86742505, compound

HRID 2231295Notes

Reaction equation

HRID 2231295 reaction equation
[CH2:1]([C:3]1([CH:23]([CH3:27])[C:24](O)=[O:25])[CH:12]2[N:7]([CH2:8][CH2:9][C:10]3[C:19]4[C:14](=[CH:15][C:16]([N+:20]([O-:22])=[O:21])=[CH:17][CH:18]=4)[NH:13][C:11]=32)[CH2:6][CH2:5][CH2:4]1)[CH3:2].CN1CCOCC1.ClC(OCC)=O.[C:41]1([C@H:47]([NH2:49])[CH3:48])[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1.C(NCC)C>C1(C)C=CC=CC=1.C(Cl)(Cl)Cl.O1CCCC1>[C:41]1([C@H:47]([NH:49][C:24](=[O:25])[CH:23]([C@@:3]2([CH2:1][CH3:2])[C@@H:12]3[N:7]([CH2:8][CH2:9][C:10]4[C:19]5[C:14](=[CH:15][C:16]([N+:20]([O-:22])=[O:21])=[CH:17][CH:18]=5)[NH:13][C:11]=43)[CH2:6][CH2:5][CH2:4]2)[CH3:27])[CH3:48])[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1

Participants

9

Reactant 5

HCID 79724-MethylmorpholineHCID 8021DiethylamineHCID 10928Ethyl chloroformateHCID 6431891-Phenethylamine, (+)-HCID 21286312HCID 21286312, compound

Product 1

HCID 86742505HCID 86742505, compoundYield 69.6%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 6212ChloroformSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

0.371 g. (0.001 mole) of (-)-()1S,12bS)-1-ethyl-10-nitro-1,2,3,4,6,7,12,12b-octahydroindolo[2,3-a]quinolizin-1-yl-propionic acid is added to a solution containing 0.111 g. (0.0011 moles) of N-methylmorpholine (redistilled from sodium) in 4 ml. of dry tetrahydrofuran while stirring under nitrogen, then the solution is cooled to 0° C. and 0.108 g. (0.001 mole) of ethyl chloroformate is rapidly added dropwise while stirring vigorously and keeping the inner temperature at or lower than 0° C. for 30 minutes, whereupon a solution containing 0.133 g. (0.0011 moles) of (R)-1-phenylethylamine in 1 ml. of dry tetrahydrofuran is dropwise added at 0° C. while stirring, finally the mixture is stirred at 0° C. for 30 minutes at room temperature for additional 4 hours. Thereupon the reaction mixture is evaporated on a rotating evaporator and after shaking thoroughly the residue with 10 ml. of dichloromethane and 5 ml. of water, the phases are separated. The dichloromethane solution is washed at first with 5 ml of 5% sodium carbonate solution, then three times with 5 ml of water each, dried over anhydrous magnesium sulphate and evaporated. The crude residue is purified by column chromatography on silica gel by using toluene containing 10% of diethylamine as eluant to give 0.33 g (69.6% yield) of the title compound, M.P.: 130°-132° C., [α]D23 =-140.5 (C=1.0 chloroform) with and Rf value of 0.43 (polygram sil G/UV 254: developed by toluene containing 10% of diethylamine: detected by UV light).

Workup

  1. additioncontaining 0.111 g
  2. customlower than 0° C.
  3. customfor 30 minutes
  4. additionwhereupon a solution containing 0.133 g
  5. stirringwhile stirring
  6. stirringfinally the mixture is stirred at 0° C. for 30 minutes at room temperature for additional 4 hours
  7. customThereupon the reaction mixture is evaporated on a rotating evaporator
  8. stirringafter shaking thoroughly the residue with 10 ml
  9. customof water, the phases are separated
  10. washThe dichloromethane solution is washed at first with 5 ml of 5% sodium carbonate solution
  11. dry with materialthree times with 5 ml of water each, dried over anhydrous magnesium sulphate
  12. customevaporated
  13. customThe crude residue is purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-7e80667ff0cb404bb6c1c08be2520e77
Source dataset
uspto-grants-1988_11
Patent number
US04782052

Reaction notes

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