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

HRID 1178401Notes

Reaction equation

HRID 1178401 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 Bashed 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. dry with materialdried over sodium sulfate
  5. customthe solvent is removed under vacuum
  6. customThe residue is chromatographically purified over silica gel with CHCl3/CH3OH (90/10)
  7. customcrystallized from diisopropyl ether

Sources & evidence

ORD record
ord-5982f67988d745b08385d1ac0a6af975
Source dataset
uspto-grants-2007_10
Patent number
US07276524B2

Reaction notes

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