Sodium Iodide → N,alpha-Bis(4-fluorophenyl)-1-(2-naphthalenylmethyl)-4-piperidinemethanamine

HRID 1614629Notes

Reaction equation

HRID 1614629 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.Br[CH2:24][C:25]1[CH:34]=[CH:33][C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH:26]=1.C(=O)([O-])[O-].[K+].[K+].[I-].[Na+]>C(O)CCC.C(Cl)Cl>[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]([CH2:24][C:25]3[CH:34]=[CH:33][C:32]4[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=4)[CH:26]=3)[CH2:12][CH2:11]2)=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 703202-BromomethylnaphthaleneHCID 19771957N,alpha-bis(4-fluorophenyl)-4-piperidinemethanamine

Product 1

HCID 19771984N,alpha-Bis(4-fluorophenyl)-1-(2-naphthalenylmethyl)-4-piperidinemethanamineYield 36%

Reagents, catalysts & solvents 2

HCID 2631-ButanolSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of N,α-bis(4-fluorophenyl)-4-piperidinemethanamine (6.47 g, 0.0214 mol), 2-(bromomethyl)naphthalene (4.74 g, 0.0214 mol), and potassium carbonate (4.84 g, 0.035 mol) was heated 16 h at reflux in 400 mL of 1-butanol containing sodium iodide (0.2 g). The reaction mixture was concentrated to dryness. The residue was partitioned with 5% sodium hydroxide. The chloroform layer was dried (Na2SO4), filtered, and concentrated to give a dark brown oil. The oil was dissolved in methylene chloride and subjected to flash chromatography. Elution was accomplished using methylene chloride, 1% acetone-methylene chloride, 2% acetone-methylene chloride, 5% acetone-methylene chloride, and 10% acetone-methylene chloride. Fractions of similar purity were combined, and solvents were removed to give a viscous gum. This material was dried in vacuo 16 h at 100° C. in the presence of phosphorus pentoxide. This procedure provided 3.40 g (36%) of white glass-like material.

Workup

  1. temperaturewas heated 16 h
  2. concentrationThe reaction mixture was concentrated to dryness
  3. customThe residue was partitioned with 5% sodium hydroxide
  4. dry with materialThe chloroform layer was dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give a dark brown oil
  8. washElution
  9. customsolvents were removed
  10. customto give a viscous gum
  11. dry with materialThis material was dried in vacuo 16 h at 100° C. in the presence of phosphorus pentoxide

Sources & evidence

ORD record
ord-9d189a31fafe41c3b1beac834fb9b664
Source dataset
uspto-grants-1993_03
Patent number
US05198449

Reaction notes

Loading…