2-Cyclopenten-1-one → HCID 19841322, compound

HRID 1638730Notes

Reaction equation

HRID 1638730 reaction equation
[C:1]([O-:4])(O)=[O:2].[Na+].[F-:6].[K+].[N+:8]([CH2:21][CH2:22][CH2:23]C)([CH2:17][CH2:18][CH2:19]C)([CH2:13][CH2:14][CH2:15][CH3:16])CCCC.[F-].C1(=[O:31])CCC=C1.[Li+].CC([N-]C(C)C)C.[N:40]1[C:49]2[C:44](=[CH:45][CH:46]=[CH:47][N:48]=2)[CH:43]=CC=1>O.CO.[Cl-].[Cl-].[Zn+2].Cl[Ti](Cl)(Cl)Cl>[CH:21]1([N:8]2[C:13]3[C:14](=[CH:15][C:16]([F:6])=[C:49]([CH:44]4[CH2:45][CH2:46][CH:47]([NH2:48])[CH2:43]4)[N:40]=3)[C:19](=[O:31])[C:18]([C:1]([OH:4])=[O:2])=[CH:17]2)[CH2:22][CH2:23]1

Participants

11

Reactant 6

HCID 135882-Cyclopenten-1-oneHCID 1360691,8-NaphthyridineHCID 516892Sodium BicarbonateHCID 522689Potassium FluorideHCID 2724141Tetrabutylammonium FluorideHCID 2724682Lithium diisopropylamide

Product 1

HCID 19841322HCID 19841322, compound

Reagents, catalysts & solvents 4

HCID 24193Titanium TetrachlorideCatalystHCID 3007855ZincchlorideCatalystHCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
65 °C

Procedure

To a stirring solution of 0.35 gram of H2NOH'HCl in 5 ml of water is added 0.42 grams of solid NaHCO3. A solution of 1.8 grams of (6) prepared from above in methyl alcohol is added to the system. After stirring for one day, the reaction mixture is concentrated. The crude material is recrystallized from ethanol. The purified oxime (1.5 grams) is placed in 40 ml of ethanol. Two grams of Raney nickel is added, and the system is placed under a hydrogen atmosphere. After one day, the catalyst is removed by filtration, and the filtrate is concentrated. The residue is dissolved in 2.5 ml of THF. While stirring this solution, 50 ml of 0.1M aqueous NaOH is added. The reaction mixture is heated at about 65° C. for four hours and concentrated. The resulting solid is slurried in 1M aqueous HCl and collected by suction filtration. The solid is rinsed with 1M aqueous HCl, ethanol, and ether. The solid is dissolved in water, and this solution is brought to pH=7 with saturated aqueous NaHCO3. The resulting free base 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(3-aminocyclopentyl)-1,8-naphthyridine-3-carboxylic acid (I) is collected by suction filtration and dried in a vacuum oven. (Z= ##STR26## A=N, R=cyclopropyl, R3 =H, R1 =OH). Alternatively, the condensation between (4) and (5) (Example 2a) may be catalyzed by other Lewis acids such as ZnCl2 or TiCl4 or sources of fluoride ion such as KF or nBu4NF. The same product may also be obtained by condensation of the dienolate derived from cyclopentenone and a strong base such as LDA with compound (1).

Workup

  1. additionis added to the system
  2. concentrationthe reaction mixture is concentrated
  3. customThe crude material is recrystallized from ethanol
  4. additionTwo grams of Raney nickel is added
  5. waitAfter one day
  6. customthe catalyst is removed by filtration
  7. concentrationthe filtrate is concentrated
  8. dissolutionThe residue is dissolved in 2.5 ml of THF
  9. stirringWhile stirring this solution, 50 ml of 0.1M aqueous NaOH
  10. additionis added
  11. concentrationconcentrated
  12. filtrationcollected by suction filtration
  13. washThe solid is rinsed with 1M aqueous HCl, ethanol, and ether
  14. dissolutionThe solid is dissolved in water
  15. filtrationThe resulting free base 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(3-aminocyclopentyl)-1,8-naphthyridine-3-carboxylic acid (I) is collected by suction filtration
  16. customdried in a vacuum oven
  17. customAlternatively, the condensation between (4) and (5) (Example 2a)
  18. customThe same product may also be obtained by condensation of the dienolate

Sources & evidence

ORD record
ord-c00b6e85b8724b55813ab85ffa75e09b
Source dataset
uspto-grants-1989_11
Patent number
US04880814

Reaction notes

Loading…