Allyl iodide → 2-Allyl-3-methyl-3-phenylbutanoic acid

HRID 1865751Notes

Reaction equation

HRID 1865751 reaction equation
[CH3:1][C:2]([CH3:13])([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[CH2:3][C:4]([OH:6])=[O:5].C(=O)=O.[CH3:17][C:18]([CH3:20])=O.C([N-]C(C)C)(C)C.[Li+].CN1CCCN(C)C1=O.C(I)C=C>O1CCCC1>[CH2:20]([CH:3]([C:2]([CH3:13])([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[CH3:1])[C:4]([OH:6])=[O:5])[CH:18]=[CH2:17]

Participants

7

Reactant 5

HCID 11166Allyl iodideHCID 13890beta-Phenylisovaleric acidHCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-HCID 2724682Lithium diisopropylamideHCID 18522661Acetone cardice

Product 1

HCID 112874162-Allyl-3-methyl-3-phenylbutanoic acidYield 64%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

In accordance with a modified literature procedure (Pfeffer, P. E.; Silbert, L. S.; Chirinko, J. M. J. Org. Chem. 37(3), 1972, 451-458), a solution of 3,3-dimethyl-3-phenyl propionic acid (0.50 g, 2.8 mmol, from Reference Example 22) in tetrahydrofuran (5 mL) is cooled to −40° C. (dry ice/acetone) while stirring under a nitrogen atmosphere. Lithium diisopropylamide (Aldrich, 2.0 M solution in tetrahydrofuran/ethylbenzene/heptane, 3.1 mL, 6.2 mmol) is added dropwise via syringe, followed by 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (DMPU, 0.37 mL, 4.2 mmol). The reaction mixture is then allowed to warm to room temperature and to stir for 30 minutes before being re-cooled to 0° C. (ice water bath). Allyl iodide (0.15 mL, 1.3 mmol) is then added neat via syringe and the reaction mixture is allowed to stir overnight while warming to room temperature. The reaction is quenched by the addition of 10% aqueous hydrochloric acid solution and extracted thrice with ethyl acetate. The combined extracts are washed twice with 10% aqueous hydrochloric acid solution and once with saturated sodium chloride solution, dried over anhydrous sodium sulfite, and concentrated under reduced pressure. Flash chromatography (silica gel, hexane/dichloromethane/ethyl acetate) is performed to give a clear blond oil (0.39 g, 64%). MS (ES−): (M−H)=217.0

Workup

  1. stirringto stir for 30 minutes
  2. stirringto stir overnight
  3. temperaturewhile warming to room temperature
  4. customThe reaction is quenched by the addition of 10% aqueous hydrochloric acid solution
  5. extractionextracted thrice with ethyl acetate
  6. washThe combined extracts are washed twice with 10% aqueous hydrochloric acid solution and once with saturated sodium chloride solution
  7. dry with materialdried over anhydrous sodium sulfite
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-cac35d8c87aa4017b1c04f8d813d1852
Source dataset
uspto-grants-2009_12
Patent number
US07626023B2

Reaction notes

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