2-Phenylisobutyric acid → 2-[4-(4-Chloro-butyryl)-phenyl]-2-methyl-propionic acid pyrrolidineamide

HRID 1836773

Reaction equation

HRID 1836773 reaction equation
[Al+3].[Cl-].[Cl-].[Cl-].[Cl:5][CH2:6][CH2:7][CH2:8][C:9](Cl)=[O:10].[CH3:12][C:13]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)([CH3:17])[C:14]([OH:16])=[O:15].[N:24]1([C:29]([NH2:31])=[O:30])[CH2:28][CH2:27][CH2:26][CH2:25]1>C(Cl)(Cl)(Cl)Cl>[N:24]1([C:29]([NH2:31])=[O:30])[CH2:28][CH2:27][CH2:26][CH2:25]1.[Cl:5][CH2:6][CH2:7][CH2:8][C:9]([C:21]1[CH:22]=[CH:23][C:18]([C:13]([CH3:17])([CH3:12])[C:14]([OH:16])=[O:15])=[CH:19][CH:20]=1)=[O:10]

Participants

6

Reactant 4

HCID 132222-Phenylisobutyric acidHCID 783704-Chlorobutyryl chlorideHCID 1383351-PyrrolidinecarboxamideHCID 6451240Aluminum(III) Chloride

Product 1

HCID 698946502-[4-(4-Chloro-butyryl)-phenyl]-2-methyl-propionic acid pyrrolidineamideYield 78%

Reagents, catalysts & solvents 1

HCID 5943Carbon TetrachlorideSolvent2×

Procedure

Add AlCl3 (8.31 g, 62.3 mmol) to carbon tetrachloride (65 mL) under a nitrogen atmosphere at room temperature. Add 4-chlorobutyryl chloride (03.5 mL, 31.2 mmol), stir for 15 minutes and add, by dropwise addition over 15 minutes, a solution of 2-methyl-2-phenyl-propionic acid, pyrrolidineamide (5.64 g, 26.0 mmol) in carbon tetrachloride (60 mL). Stir at room temperature for 17 hours, pour into ice water (100 mL) and separate the layers. Wash the aqueous layer with methylene chloride (2×70 mL), 5% aqueous sodium hydrogen carbonate, combine the organic layers and dry (Na2SO4). Filter, evaporate the filtrate in vacuo and purify by silica gel chromatography (5:2 hexane/ethyl acetate) to give the title compound (6.559, 78%) as a light yellow oil.

Workup

  1. additionadd, by dropwise addition over 15 minutes
  2. customseparate the layers
  3. washWash the aqueous layer with methylene chloride (2×70 mL), 5% aqueous sodium hydrogen carbonate
  4. dry with materialdry (Na2SO4)
  5. filtrationFilter
  6. customevaporate the filtrate in vacuo
  7. custompurify by silica gel chromatography (5:2 hexane/ethyl acetate)

Sources & evidence

ORD record
ord-c661aa5fc1944b339fb70ceea8a1b969
Source dataset
uspto-grants-2004_08
Patent number
US06777555B2

Linked notes

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