Hydrochloric Acid → HCID 19772045, compound

HRID 1614634Notes

Reaction equation

HRID 1614634 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][CH:9]([C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=2)[CH:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)=[CH:4][CH:3]=1.[CH2:23](Br)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C(=O)(O)[O-].[Na+].[ClH:36]>C(#N)C.C(Cl)Cl.C(O)C.C(OCC)C>[ClH:36].[ClH:36].[F:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][CH:9]([C:16]2[CH:17]=[CH:18][C:19]([F:22])=[CH:20][CH:21]=2)[CH:10]2[CH2:15][CH2:14][N:13]([CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[CH2:12][CH2:11]2)=[CH:6][CH:7]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 7498Benzyl BromideHCID 516892Sodium BicarbonateHCID 19771957N,alpha-bis(4-fluorophenyl)-4-piperidinemethanamine

Product 1

HCID 19772045HCID 19772045, compoundYield 36.7%

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolventHCID 21585056Diethyl ether ethanolSolvent

Procedure

A mixture of N,α-bis(4-fluorophenyl)-4-piperidinemethanamine (3.30 g, 0.0109 mol), benzylbromide (1.86 g, 0.0109 mol), and sodium bicarbonate (1.68 g, 0.02 mol) was stirred 16 h at room temperature in 300 mL of acetonitrile (dried over 4 A molecular sieves) containing sodium iodide (0.2 g). The mixture was then heated at reflux 16 h followed by stirring 72 h at room temperature. The reaction was stripped to dryness and partitioned between chloroform and water. The chloroform layer was extracted with 5% sodium hydroxide and dried (Na2SO4). The chloroform was removed to give a fluffy-brown residue. This material was dissolved in methylene chloride for flash chromatography on a silica gel column. Elution was accomplished using 1% acetone in methylene chloride, 3% acetone in methylene chloride, and 5% acetone in methylene chloride. Fractions of similar purity were combined, and solvents removed to give an oil. This oil was converted to the HCl salt in an ethanol-diethyl ether mixture. The white solid obtained was then recrystallized from methanol-diethyl ether to give a white solid. The solid was dried 16 h at 78° C. in the presence of phosphorus pentoxide. This method provided 1.86 g (36.7%) of white crystalline solid, mp 241°-242° C. (dec.).

Workup

  1. customdried over 4 A molecular sieves)
  2. additioncontaining sodium iodide (0.2 g)
  3. temperatureThe mixture was then heated
  4. temperatureat reflux 16 h
  5. custompartitioned between chloroform and water
  6. extractionThe chloroform layer was extracted with 5% sodium hydroxide
  7. dry with materialdried (Na2SO4)
  8. customThe chloroform was removed
  9. customto give a fluffy-brown residue
  10. washElution
  11. customsolvents removed
  12. customto give an oil
  13. customThe white solid obtained
  14. customwas then recrystallized from methanol-diethyl ether
  15. customto give a white solid
  16. dry with materialThe solid was dried 16 h at 78° C. in the presence of phosphorus pentoxide

Sources & evidence

ORD record
ord-c0e6e9175c7d447dab10a453d9bf84fc
Source dataset
uspto-grants-1993_03
Patent number
US05198449

Reaction notes

Loading…