4-Fluorophenyl isocyanate → HCID 12148995, compound

HRID 1836403Notes

Reaction equation

HRID 1836403 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:14]=[CH:15][CH:16]=1)[C:5]([CH:7]1[CH2:12][CH2:11][N:10]([CH3:13])[CH2:9][CH2:8]1)=[O:6].[F:17][C:18]1[CH:23]=[CH:22][C:21]([N:24]=[C:25]=[O:26])=[CH:20][CH:19]=1>C(Cl)Cl.C(O)(=O)C.CO>[F:17][C:18]1[CH:23]=[CH:22][C:21]([NH:24][C:25](=[O:26])[NH:1][C:2]2[CH:3]=[C:4]([CH:14]=[CH:15][CH:16]=2)[C:5]([CH:7]2[CH2:8][CH2:9][N:10]([CH3:13])[CH2:11][CH2:12]2)=[O:6])=[CH:20][CH:19]=1

Participants

6

Reactant 2

HCID 709554-Fluorophenyl isocyanateHCID 101306514-[3-Aminobenzoyl]-1-methylpiperidine

Product 1

HCID 12148995HCID 12148995, compoundYield 67%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

4-[3-aminobenzoyl]-1-methylpiperidine (25 mg, 0.115 mmol) and 4-fluorophenyl isocyanate (39 μL, 0.344 mmol) in methylene chloride (2 mL) were mixed for 72 h at ambient temperature. The solution was diluted with 10% acetic acid in methanol and poured over a Varian Mega Bond Elut™ strong cation exchange column. The column was rinsed extensively with methanol to remove impurities, then treated with a 2M ammonia in methanol to elute the product from the column. The solvent was evaporated and the residue was stirred with 5N sodium hydroxide solution (1 mL). The solvent was removed under vacuum and the residue was purified by silica gel chromatography (methylene chloride:methanol:ammonium hydroxide, 97.5:2.5:0.25 then 95:5:0.5). The solvent was evaporated to give 27.4 mg (67%) of the title compound.

Workup

  1. additionpoured over a Varian Mega Bond Elut™ strong cation exchange column
  2. washThe column was rinsed extensively with methanol
  3. customto remove impurities
  4. additiontreated with a 2M ammonia in methanol
  5. washto elute the product from the column
  6. customThe solvent was evaporated
  7. customThe solvent was removed under vacuum
  8. customthe residue was purified by silica gel chromatography (methylene chloride
  9. customThe solvent was evaporated

Sources & evidence

ORD record
ord-d0416380f380412db0053a6092df0a8e
Source dataset
uspto-grants-2004_08
Patent number
US06777428B1

Reaction notes

Loading…