Benzoyl chloride → 1-Benzoyl-N,alpha-bis(4-fluorophenyl)-4-piperidinemethanamine

HRID 1614632Notes

Reaction equation

HRID 1614632 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.C(N(CC)CC)C.[C:30](Cl)(=[O:37])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1>C(Cl)Cl>[C:30]([N:13]1[CH2:14][CH2:15][CH:10]([CH:9]([C:16]2[CH:17]=[CH:18][C:19]([F:22])=[CH:20][CH:21]=2)[NH:8][C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=2)[CH2:11][CH2:12]1)(=[O:37])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1

Participants

5

Reactant 3

HCID 7412Benzoyl chlorideHCID 8471TriethylamineHCID 19771957N,alpha-bis(4-fluorophenyl)-4-piperidinemethanamine

Product 1

HCID 197719491-Benzoyl-N,alpha-bis(4-fluorophenyl)-4-piperidinemethanamine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of N,α-bis(4-fluorophenyl)-4-piperidinemethanamine (3.21 g, 0.0106 mol), triethylamine (2.5 g, 0.025 mol), and benzoyl chloride (1.70 g, 0.012 mol) in 400 mL of methylene chloride was stirred 16 h at room temperature. The reaction was concentrated to dryness and dissolved in chloroform. The chloroform layer was extracted successively with water, 1N sulfuric acid, and 5% sodium hydroxide. The chloroform layer was dried (Na2SO4) and filtered. The chloroform was removed to give a fluffy-white residue. This material was dissolved in methylene chloride and chromatographed by flash chromatography on silica gel. Elution was accomplished using methylene chloride, 1% acetone-methylene chloride, 2% acetone-methylene chloride, and 4% acetone-methylene chloride. Fractions of similar purity were combined, and solvents removed to give a fluffy-white residue. This material was triturated with isopropyl ether and chilled in a freezer. A white solid was isolated and dried, 16 h at 78° C. This furnished 1.40 g (32.5%) of white crystalline solid, mp 157°-158° C.

Workup

  1. concentrationThe reaction was concentrated to dryness
  2. dissolutiondissolved in chloroform
  3. extractionThe chloroform layer was extracted successively with water, 1N sulfuric acid, and 5% sodium hydroxide
  4. dry with materialThe chloroform layer was dried (Na2SO4)
  5. filtrationfiltered
  6. customThe chloroform was removed
  7. customto give a fluffy-white residue
  8. customchromatographed by flash chromatography on silica gel
  9. washElution
  10. customsolvents removed
  11. customto give a fluffy-white residue
  12. customThis material was triturated with isopropyl ether
  13. temperaturechilled in a freezer
  14. customA white solid was isolated
  15. customdried, 16 h at 78° C

Sources & evidence

ORD record
ord-a917f4ce311d4b919fba4ffe41a4c87b
Source dataset
uspto-grants-1993_03
Patent number
US05198449

Reaction notes

Loading…