Borane → HCID 53788672, compound

HRID 1720314Notes

Reaction equation

HRID 1720314 reaction equation
[CH:1]([O:4][C:5]([C:7]1[N:8]=[CH:9][C:10]2[N:11](C(OC(C)(C)C)=O)[C:12]3[C:17]([C:18]=2[C:19]=1[CH2:20][O:21][CH3:22])=[C:16](OS(C(F)(F)F)(=O)=O)[CH:15]=[CH:14][CH:13]=3)=[O:6])([CH3:3])[CH3:2].C(B(CC)[C:41]1[CH:42]=[N:43][CH:44]=[CH:45][CH:46]=1)C.[Cl-].[Li+].C(=O)([O-])[O-].[Na+].[Na+].B>C1(C)C=CC=CC=1.[Pd].[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O.C(O)C>[CH:1]([O:4][C:5]([C:7]1[N:8]=[CH:9][C:10]2[NH:11][C:12]3[C:17]([C:18]=2[C:19]=1[CH2:20][O:21][CH3:22])=[C:16]([C:41]1[CH:42]=[N:43][CH:44]=[CH:45][CH:46]=1)[CH:15]=[CH:14][CH:13]=3)=[O:6])([CH3:2])[CH3:3]

Participants

11

Reactant 5

HCID 6331BoraneHCID 10340Sodium CarbonateHCID 433294Lithium Chloride2×HCID 6428513-(Diethylboryl)pyridineHCID 56982795HCID 56982795, compound

Product 1

HCID 53788672HCID 53788672, compound

Reagents, catalysts & solvents 5

HCID 23938PalladiumCatalystHCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 702EthanolSolvent2×HCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

532 mg of 5-trifluoromethanesulfonyloxy-4-methoxymethyl-9- tert.butoxycarbonyl-β-carboline-3-carboxylic acid isopropyl ester is mixed in 20 ml of toluene in succession with 164 mg of diethyl-3-pyridylborane, 36 mg of tetrakis (triphenylphosphine) palladium (O), 84 mg of lithium chloride, 4 ml of ethanol as well as 2 ml of a 2-m aqueous sodium carbonate solution and refluxed for 3.5 hours. Then borane, palladium catalyst, ethanol, lithium chloride as well as soda solution are added again and heated for 3.5 hours to 120° C. solution temperature. Then it is mixed with 30 ml of water and extracted three times with 30 ml of ethyl acetate. The organic phase is dried, filtered and concentrated by evaporation. The residue is stirred with 13 ml of trifluoroacetate acid for 1 hour at room temperature. After concentration by evaporation it is taken up in 50 ml of dilute sodium carbonate solution and extracted three times with 30 ml of ethyl acetate. The organic phase is washed with water, dried, filtered and concentrated by evaporation. The residue is chromatographed successively twice on silica gel, first with eluant methylene chloride:ethanol=10:1 and then the corresponding fractions on a second column with toluene: glacial acetic acid: water=10:1:1. The corresponding combined fractions are concentrated by evaporation and the residue is refluxed for 1.5 hours with 10 ml of isopropanol and 45 mg of titanium (IV) isopropylate. After concentration by evaporation it is taken up in 15 ml of 1-N hydrochloric acid and extracted three times with 30 ml of ethyl acetate each. The combined organic phase is discarded. The aqueous phase is made alkaline with ammonia and extracted three times with ethyl acetate. The organic phase is dried, filtered and concentrated by evaporation and 45 mg (12% of theory) of 5-(3-pyridyl)-4-methoxymethyl-β-carboline-3-carboxylic acid isopropyl ester with a melting point of 187°-188° C. is obtained.

Workup

  1. temperaturerefluxed for 3.5 hours
  2. temperatureheated for 3.5 hours to 120° C. solution temperature
  3. extractionextracted three times with 30 ml of ethyl acetate
  4. customThe organic phase is dried
  5. filtrationfiltered
  6. concentrationconcentrated by evaporation
  7. concentrationAfter concentration
  8. customby evaporation it
  9. extractionextracted three times with 30 ml of ethyl acetate
  10. washThe organic phase is washed with water
  11. customdried
  12. filtrationfiltered
  13. concentrationconcentrated by evaporation
  14. customThe residue is chromatographed successively twice on silica gel, first with eluant methylene chloride
  15. concentrationThe corresponding combined fractions are concentrated by evaporation
  16. temperaturethe residue is refluxed for 1.5 hours with 10 ml of isopropanol and 45 mg of titanium (IV)
  17. concentrationAfter concentration
  18. customby evaporation it
  19. extractionextracted three times with 30 ml of ethyl acetate each
  20. extractionextracted three times with ethyl acetate
  21. customThe organic phase is dried
  22. filtrationfiltered
  23. concentrationconcentrated by evaporation and 45 mg (12% of theory) of 5-(3-pyridyl)-4-methoxymethyl-β-carboline-3-carboxylic acid isopropyl ester with a melting point of 187°-188° C.
  24. customis obtained

Sources & evidence

ORD record
ord-28c280b29b9347b88d00548b49a17c97
Source dataset
uspto-grants-1996_04
Patent number
US05506234

Reaction notes

Loading…