Potassium Phosphate, Tribasic → Ethyl 4-[3-(3-fluoroquinolin-4-yl)propyl]-1-(tert-butyloxycarbonyl)piperidine-4-carboxylate

HRID 395005Notes

Reaction equation

HRID 395005 reaction equation
[CH2:1]([C:4]1([C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:6][CH2:5]1)[CH:2]=[CH2:3].C12BC(CCC1)CCC2.[F:31][C:32]1[CH:33]=[N:34][C:35]2[C:40]([C:41]=1I)=[CH:39][CH:38]=[CH:37][CH:36]=2.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCCC1.[Cl-].C1(P([C-]2C=CC=C2)C2C=CC=CC=2)C=CC=CC=1.[CH-]1C=CC=C1.[Fe+2].[Pd+2].[Cl-]>[F:31][C:32]1[CH:33]=[N:34][C:35]2[C:40]([C:41]=1[CH2:3][CH2:2][CH2:1][C:4]1([C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:15])([CH3:16])[CH3:14])=[O:11])[CH2:6][CH2:5]1)=[CH:39][CH:38]=[CH:37][CH:36]=2

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 789669-Borabicyclo(3.3.1)nonaneHCID 111084963-Fluoro-4-iodoquinolineHCID 162182701-tert-Butyl 4-ethyl 4-(prop-2-en-1-yl)piperidine-1,4-dicarboxylate

Product 1

HCID 69682605Ethyl 4-[3-(3-fluoroquinolin-4-yl)propyl]-1-(tert-butyloxycarbonyl)piperidine-4-carboxylateYield 56.9%

Reagents, catalysts & solvents 2

HCID 178478644HCID 178478644, compoundCatalystHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
70 °C

Procedure

17.7 g of ethyl 4-allyl-1-(tert-butyloxycarbonyl)piperidine-4-carboxylate in 200 cm3 of tetrahydrofuran were cooled to a temperature in the region of −30° C. and 135 cm3 of a 0.5M solution of 9-borabicyclo-[3.3.1]nonane in tetrahydrofuran were added with stirring and under an inert atmosphere. After the addition, the temperature of the mixture was returned to about 20° C. and the mixture was stirred for 2 hours. 14.8 g of 3-fluoro-4-iodoquinoline in 430 cm3 of tetrahydrofuran, 1.3 g of palladium diphenylphosphinoferrocene chloride and 29.8 g of tribasic potassium phosphate were added. The reaction mixture was then heated at a temperature in the region of 70° C. for 20 hours. After cooling to a temperature in the region of 20° C., the reaction mass was filtered and washed with 3 times 100 cm3 of tetrahydrofuran. The filtrate was concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. The evaporation residue was taken up in 500 cm3 of diethyl ether, the insoluble material was washed with 3 times 100 cm3 of diethyl ether and the filtrate was concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. The oil obtained was purified by chromatography under atmospheric pressure, on a column of silica gel (particle size 20-45μ; diameter 6 cm; height 45 cm), eluting with a dichloromethane/ethyl acetate mixture (90/10 by volume) and collecting 120-cm3 fractions. Fractions 30 to 76 were combined and then concentrated to dryness under the same conditions as above. 13.7 g of ethyl 4-[3-(3-fluoroquinolin-4-yl)propyl]-1-(tert-butyloxycarbonyl)-piperidine-4-carboxylate were obtained in the form of a viscous orange-colored oil.

Workup

  1. additionwere added
  2. additionAfter the addition
  3. customwas returned to about 20° C.
  4. stirringthe mixture was stirred for 2 hours
  5. temperatureAfter cooling to a temperature in the region of 20° C.
  6. filtrationthe reaction mass was filtered
  7. washwashed with 3 times 100 cm3 of tetrahydrofuran
  8. concentrationThe filtrate was concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C
  9. washthe insoluble material was washed with 3 times 100 cm3 of diethyl ether
  10. concentrationthe filtrate was concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C
  11. customThe oil obtained
  12. customwas purified by chromatography under atmospheric pressure, on a column of silica gel (particle size 20-45μ; diameter 6 cm; height 45 cm)
  13. washeluting with a dichloromethane/ethyl acetate mixture (90/10 by volume)
  14. customcollecting 120-cm3 fractions
  15. concentrationconcentrated to dryness under the same conditions as above

Sources & evidence

ORD record
ord-4910b5431f4e4491b94a708b59cd847d
Source dataset
uspto-grants-2003_08
Patent number
US06603005B2

Reaction notes

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