Ethanol → HCID 70605679, compound

HRID 614859Notes

Reaction equation

HRID 614859 reaction equation
Cl([O-])(=O)(=O)=O.[CH2:6]([C@:8]1([CH:26]=[C:27]([O:32][CH3:33])[C:28]([O:30][CH3:31])=[O:29])[C:17]2[C:16]3[NH:18][C:19]4[C:24]([C:15]=3[CH2:14][CH2:13][N+:12]=2[CH2:11][CH2:10][CH2:9]1)=[CH:23][C:22]([F:25])=[CH:21][CH:20]=4)[CH3:7].C([O-])(=O)C.[K+].C(O)C.[H][H]>C(Cl)Cl.C(O)C.[Pd].O>[CH3:31][O:30][C:28](=[O:29])[C:27]([O:32][CH3:33])=[CH:26][C@@:8]1([CH2:6][CH3:7])[C@@H:17]2[N:12]([CH2:13][CH2:14][C:15]3[C:24]4[C:19](=[CH:20][CH:21]=[C:22]([F:25])[CH:23]=4)[NH:18][C:16]=32)[CH2:11][CH2:10][CH2:9]1

Participants

8

Reactant 4

HCID 702EthanolHCID 517044Potassium AcetateHCID 86736430HCID 86736430, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 70605679HCID 70605679, compound

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 962WaterSolventHCID 21584144Dichloromethane ethanolSolvent

Procedure

The E and Z isomer mixture of (S)-1-ethyl-9-fluoro-1-(2-methoxy-2-methoxycarbonylvinyl)-2,3,4,6,7,12-hexahydro-1H-indolo[2,3-a]quinolizin-5-ium perchlorate is dissolved at 30° in 10 cc of methylene chloride/ethanol (80:20), and the solution is added to a prehydrogenated mixture of 982 mg of potassium acetate, 2 g of 10% Pd on charcoal and 8 cc of ethanol, as well as 2 cc of water. The mixture is then hydrogenated at room temperature and normal pressure, while stirring, until 8 millimols of hydrogen have been taken up and hydrogen consumption practically stops. After filtering through Hyflo, and washing with 20 cc of methylene chloride/ethanol (80:20), the filtrate is concentrated by evaporation at 30°/20 mm, the residue is dissolved in 20 cc of methylene chloride, mixed at 0° with 20 cc of 2 N ammonia and divided. The organic phase is separated, extracted with 10 cc of methylene chloride, the 1st and 2nd methylene chloride phases are washed with 20 cc of the same water, combined and dried with sodium sulphate. The reaction mixture is concentrated by evaporation at 30°/20 mm, pulverized, and dried in a high vacuum, whereby a mixture of the Z and E isomers of 3-[(1S,12bS)-1-ethyl-9-fluoro-1,2,3,4,6,7,12,12b-octahydro-indolo[2,3-a]quinolizin-1-yl]-2-methoxy-propenoic acid methyl ester is obtained in crude form as yellow-brown residue.

Workup

  1. customis then hydrogenated at room temperature
  2. customhydrogen consumption
  3. filtrationAfter filtering through Hyflo
  4. washwashing with 20 cc of methylene chloride/ethanol (80:20)
  5. concentrationthe filtrate is concentrated by evaporation at 30°/20 mm
  6. dissolutionthe residue is dissolved in 20 cc of methylene chloride
  7. additionmixed at 0° with 20 cc of 2 N ammonia
  8. customThe organic phase is separated
  9. extractionextracted with 10 cc of methylene chloride
  10. washthe 1st and 2nd methylene chloride phases are washed with 20 cc of the same water
  11. dry with materialdried with sodium sulphate
  12. concentrationThe reaction mixture is concentrated by evaporation at 30°/20 mm
  13. customdried in a high vacuum, whereby
  14. additiona mixture of the Z and E isomers of 3-[(1S,12bS)-1-ethyl-9-fluoro-1,2,3,4,6,7,12,12b-octahydro-indolo[2,3-a]quinolizin-1-yl]-2-methoxy-propenoic acid methyl ester
  15. customis obtained in crude form as yellow-brown residue

Sources & evidence

ORD record
ord-92bad73e01bf43a29037be4b3d885a22
Source dataset
uspto-grants-1979_03
Patent number
US04146643

Reaction notes

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