Potassium Iodide → 1-[4-[2-[4-[Bis(4-fluorophenyl)methyl]-1-piperidinyl]ethoxy]-3-methoxyphenyl]ethanone

HRID 1193693Notes

Reaction equation

HRID 1193693 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:15]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=2)[CH:9]2[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)=[CH:4][CH:3]=1.Cl[CH2:23][CH2:24][O:25][C:26]1[CH:31]=[CH:30][C:29]([C:32](=[O:34])[CH3:33])=[CH:28][C:27]=1[O:35][CH3:36].C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>C(O)CCC.CCCCCC.C(OCC)(=O)C.C(Cl)(Cl)Cl>[F:21][C:18]1[CH:17]=[CH:16][C:15]([CH:8]([C:5]2[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=2)[CH:9]2[CH2:14][CH2:13][N:12]([CH2:23][CH2:24][O:25][C:26]3[CH:31]=[CH:30][C:29]([C:32](=[O:34])[CH3:33])=[CH:28][C:27]=3[O:35][CH3:36])[CH2:11][CH2:10]2)=[CH:20][CH:19]=1

Participants

8

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 132505444-[Bis(4-fluorophenyl)methyl]piperidineHCID 144071701-[4-(2-Chloroethoxy)-3-methoxyphenyl]ethanone

Product 1

HCID 144071251-[4-[2-[4-[Bis(4-fluorophenyl)methyl]-1-piperidinyl]ethoxy]-3-methoxyphenyl]ethanoneYield 27%

Reagents, catalysts & solvents 3

HCID 2631-ButanolSolventHCID 6212ChloroformSolventHCID 21226206Ethyl acetate hexaneSolvent

Procedure

A mixture of 4-[bis(4-fluorophenyl)methyl]piperidine, 4.88 g (0.017 mole), 1-[4-(2-chloroethoxy)-3-methoxyphenyl]ethanone, 3.86 g (0.017 mole), and potassium carbonate, 5.53 g (0.04 mole) was heated overnight at gentle reflux in 350 ml of 1-butanol containing potassium iodide (0.3 g). The reaction mixture was filtered and stripped to dryness. The dark brown oil obtained was dissolvedin chloroform and extracted with 1N sulfuric acid and 5% sodium hydroxide. The chloroform layer was dried, filtered, and solvent removed. This furnished a brown oil which was subjected to flash chromatography on silica gel using hexane-ethyl acetate for elution. A white solid was obtained by evaporating the fractions containing the product. The solid was extracted with diethyl ether and the mixture was placed in the freezer overnight. A white solid was obtained which was dried at 80° C. in vacuo overnight. A yield of 2.2 g (27%) of white crystalline solid, m.p. 129°-131° C. was obtained.

Workup

  1. temperaturewas heated overnight
  2. filtrationThe reaction mixture was filtered
  3. customThe dark brown oil obtained
  4. extractionextracted with 1N sulfuric acid and 5% sodium hydroxide
  5. dry with materialThe chloroform layer was dried
  6. filtrationfiltered
  7. customsolvent removed
  8. customThis furnished a brown oil which
  9. washfor elution
  10. customA white solid was obtained
  11. customby evaporating the fractions
  12. additioncontaining the product
  13. extractionThe solid was extracted with diethyl ether
  14. customwas placed in the freezer overnight
  15. customA white solid was obtained which
  16. customwas dried at 80° C. in vacuo overnight

Sources & evidence

ORD record
ord-adee6465a1dc4e8cae0925dd1726624f
Source dataset
uspto-grants-1989_03
Patent number
US04810713

Reaction notes

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