HCID 23150770, compound → HCID 11978506, compound

HRID 908901Notes

Reaction equation

HRID 908901 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5](/[CH:8]=[CH:9]/[CH2:10][O:11][CH2:12][CH2:13][CH2:14][N:15]2[CH2:19][CH2:18][CH2:17][CH2:16]2)=[CH:4][CH:3]=1>CN(C)C=O.[Pt](=O)=O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][O:11][CH2:12][CH2:13][CH2:14][N:15]2[CH2:16][CH2:17][CH2:18][CH2:19]2)=[CH:4][CH:3]=1

Participants

4

Reactant 1

HCID 23150770HCID 23150770, compound

Product 1

HCID 11978506HCID 11978506, compoundYield 28.9%

Reagents, catalysts & solvents 2

HCID 345198Adams' catalystCatalyst2×HCID 6228DimethylformamideSolvent

Procedure

A suspension of platinum dioxide (300 mg) in a solution of trans-1-{3-[3-(4-fluorophenyl)allyloxy]propyl}pyrrolidine (330 mg) in N,N-dimethylformamide (3 mL) is stirred overnight at room temperature under an atmosphere of dihydrogene. An additional amount of platinum dioxide is added and the suspension is stirred for 24 hours at room temperature under an atmosphere of dihydrogene. The suspension is filtered over a celite pad and rinsed with ethyl acetate. Ethyl acetate is evaporated from the filtrate, platinum hydroxide (190 mg) is added and the suspension is stirred for 48 hours at room temperature under an atmosphere of dihydrogene. The suspension is filtered over a celite pad, rinsed with ethyl acetate, concentrated under reduced pressure and dissolved in a mixture of ethanol (2 mL) and diethyl oxide (200 μL). A solution of oxalic acid (58 mg) in ethanol (2 mL) is added. The mixture is concentrated under reduced pressure and suspended in diethyl oxide. The precipitate is filtered, rinsed with diethyl ether, dissolved in water (5 mL). The aqueous layer is made alkaline with ammonia and extracted twice with diethyl oxide (10 mL). The organic extracts are pooled, dried over magnesium sulphate, concentrated under reduced pressure and purified by chromatography over silica gel with a gradient dichloromethane/methanol/ammonia from 99/10/0.1 to 92/2/0.2. Fractions containing the expected product are pooled, concentrated under reduced pressure, dissolved in diethyl oxide (2 mL). A solution of oxalic acid (21 mg) in acetone is added and the precipitate that appears is filtered and dried under reduced pressure at 40° C. under a film of diethyl oxide to give 96 mg of 1-{3-[3-(4-fluorophenyl)propoxy]propyl}pyrrolidine, oxalate as a white solid melting at 106° C.

Workup

  1. stirringthe suspension is stirred for 24 hours at room temperature under an atmosphere of dihydrogene
  2. filtrationThe suspension is filtered over a celite pad
  3. washrinsed with ethyl acetate
  4. customEthyl acetate is evaporated from the filtrate, platinum hydroxide (190 mg)
  5. additionis added
  6. stirringthe suspension is stirred for 48 hours at room temperature under an atmosphere of dihydrogene
  7. filtrationThe suspension is filtered over a celite pad
  8. washrinsed with ethyl acetate
  9. concentrationconcentrated under reduced pressure
  10. dissolutiondissolved in a mixture of ethanol (2 mL) and diethyl oxide (200 μL)
  11. additionA solution of oxalic acid (58 mg) in ethanol (2 mL) is added
  12. concentrationThe mixture is concentrated under reduced pressure
  13. filtrationThe precipitate is filtered
  14. washrinsed with diethyl ether
  15. dissolutiondissolved in water (5 mL)
  16. extractionextracted twice with diethyl oxide (10 mL)
  17. dry with materialdried over magnesium sulphate
  18. concentrationconcentrated under reduced pressure
  19. custompurified by chromatography over silica gel with a gradient dichloromethane/methanol/ammonia from 99/10/0.1 to 92/2/0.2
  20. additionFractions containing the expected product
  21. concentrationconcentrated under reduced pressure
  22. dissolutiondissolved in diethyl oxide (2 mL)
  23. additionA solution of oxalic acid (21 mg) in acetone is added
  24. filtrationthe precipitate that appears is filtered
  25. dry with materialdried under reduced pressure at 40° C. under a film of diethyl oxide

Sources & evidence

ORD record
ord-59e8764450384e549bccb342e2cdc3db
Source dataset
uspto-grants-2011_09
Patent number
US08017646B2

Reaction notes

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