Benzyl Bromide → 2-Benzyl-3-methyl-3-phenylbutanoic acid

HRID 133843

Reaction equation

HRID 133843 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.CC(C)=O.C([N-]C(C)C)(C)C.[Li+].CN1CCCN(C)C1=O.[CH2:38](Br)[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1>O1CCCC1>[CH2:38]([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])[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1

Participants

7

Reactant 5

HCID 7498Benzyl BromideHCID 13890beta-Phenylisovaleric acidHCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-HCID 2724682Lithium diisopropylamideHCID 18522661Acetone cardice

Product 1

HCID 114029312-Benzyl-3-methyl-3-phenylbutanoic acid

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 (0.22 g, 1.2 mmol, from Reference Example 22) in tetrahydrofuran (2 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, 1.4 mL, 2.8 mmol) is added dropwise via syringe, followed by 1,3-dimethyl-3,4,5,6-tetrahydro-2(1 H)-pyrimidinone (DMPU, 0.16 mL, 1.3 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). Benzyl bromide (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, ether/hexanes) is performed to give a straw colored gum (0.91 g, 70% for two combined reactions). MS (ES−): (M−H)=266.9

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
  9. customto give a straw colored gum (0.91 g, 70% for two combined reactions)

Sources & evidence

ORD record
ord-743c26e1cbad42f2bb0a1badec3b8697
Source dataset
uspto-grants-2008_06
Patent number
US07390910B2

Linked notes

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