Diphenylphosphinic chloride → N-[4-(1-diphenylphosphinyl-piperidin-4-yl)-butyl]-3-(pyridin-3-yl)-propionamide

HRID 1278962Notes

Reaction equation

HRID 1278962 reaction equation
[C:1]1([P:7](Cl)([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH:16]1[CH2:21][CH2:20][CH:19]([CH2:22][CH2:23][CH2:24][CH2:25][NH:26][C:27](=[O:36])[CH2:28][CH2:29][C:30]2[CH:31]=[N:32][CH:33]=[CH:34][CH:35]=2)[CH2:18][CH2:17]1>C1COCC1>[C:1]1([P:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)([N:16]2[CH2:21][CH2:20][CH:19]([CH2:22][CH2:23][CH2:24][CH2:25][NH:26][C:27](=[O:36])[CH2:28][CH2:29][C:30]3[CH:31]=[N:32][CH:33]=[CH:34][CH:35]=3)[CH2:18][CH2:17]2)=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

4

Reactant 2

HCID 73910Diphenylphosphinic chlorideHCID 18425707N-(4-piperidin-4-yl-butyl)-3-(pyridin-3-yl)-propionamide

Product 1

HCID 18431541N-[4-(1-diphenylphosphinyl-piperidin-4-yl)-butyl]-3-(pyridin-3-yl)-propionamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

3.4 ml (17.3 mmol) diphenylphosphinic acid chloride are dissolved in 100 ml absolute THF and cooled to ca. 0° C. under moisture exclusion. 5.0 g (17.3 mmol) N-(4-piperidin-4-yl-butyl)-3-(pyridin-3-yl)-propionamide and 4.8 ml (34.6 mmol) TEA are dissolved in 50 ml absolute THF and added dropwise under ice cooling. The mixture is stirred for three days at RT without further cooling. Subsequently, the solvent is removed under vacuum to a large extent and the residue is taken up in 100 ml 10% sodium hydroxide solution and extracted twice, each with 150 ml CHCl3. The combined organic phases are washed with saturated NaCl-solution, dried over sodium sulfate and the solvent is removed under vacuum. The residue is chromatographically purified over silica gel with CHCl3/CH3OH (90/10) and crystallized from diisopropyl ether after drawing off the solvent. Colorless crystals with an MP of 134-135° C. yield 5.3 g (62%).

Workup

  1. additionadded dropwise under ice cooling
  2. customSubsequently, the solvent is removed under vacuum to a large extent
  3. extractionextracted twice
  4. washThe combined organic phases are washed with saturated NaCl-solution
  5. dry with materialdried over sodium sulfate
  6. customthe solvent is removed under vacuum
  7. customThe residue is chromatographically purified over silica gel with CHCl3/CH3OH (90/10)
  8. customcrystallized from diisopropyl ether

Sources & evidence

ORD record
ord-49a857db90954798a7d19c875b538177
Source dataset
uspto-grants-2002_09
Patent number
US06444823B1

Reaction notes

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