1-Bromo-3-methylbutane → Methyl 3-isobutyl-benzoate

HRID 1666582Notes

Reaction equation

HRID 1666582 reaction equation
BrC[CH2:3][CH:4]([CH3:6])[CH3:5].[CH3:7][O:8][C:9](=[O:17])[C:10]1[CH:15]=[CH:14][CH:13]=[C:12](Br)[CH:11]=1>C1COCC1.O.[Zn+2].[Br-].[Br-]>[CH2:3]([C:12]1[CH:11]=[C:10]([CH:15]=[CH:14][CH:13]=1)[C:9]([O:8][CH3:7])=[O:17])[CH:4]([CH3:6])[CH3:5]

Participants

6

Reactant 2

HCID 78911-Bromo-3-methylbutaneHCID 12070Methyl 3-bromobenzoate

Product 1

HCID 20771995Methyl 3-isobutyl-benzoateYield 97.1%

Reagents, catalysts & solvents 3

HCID 10421208Zinc bromideCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

In an oven-dried round bottom flask Mg turnings (1.13 g, 46.6 mmol) are suspended in THF (1 mL). 1-Bromo-3-methylbutane (6.37 g, 46.5 mmol) is carefully added while the mixture is initially heated to reflux. The mixture is stirred for approximately 30 min until the Mg has dissolved. The mixture is then added to a cold (5° C.) solution of ZnBr2 (10.47 g, 46.5 mmol) in THF (80 mL). The thick suspension is stirred at 0° C. for 20 min before it is cooled to −75° C. 1,1′-bis(diphenylphosphino)ferrocene-palladium(II) dichloride dichloromethane complex (184 mg, 0.225 mmol) followed by methyl-3-bromobenzoate (5.0 g, 23.3 mmo) is then added. The mixture is warmed to rt and stirred for 24 h. The reaction mixture is diluted with water and extracted with EA. The org. extract is dried over MgSO4, filtered and evaporated. The crude product is purified by CC on silica gel eluting with heptane:EA 20:1 to give methyl 3-isobutyl-benzoate (4.34 g) as a colourless oil. This material is dissolved in methanol (50 mL) and 2 N aq. LiOH (10 mL) and stirred at rt for 16 h. The mixture is acidified by adding 1 N aq. HCl and extracted with EA. The org. extracts are dried over MgSO4, filtered and evaporated to give 3-isobutyl-benzoic acid (3.84 g) as a colourless oil; LC-MS: tR=0.91 min; 1H NMR (CDCl3): δ 0.87 (d, J=6.7 Hz, 6H), 1.77-1.94 (m, 1H), 2.48 (d, J=7.0 Hz, 2H), 7.29-7.35 (m, 2H), 7.86 (s, 1H), 7.88-7.94 (m, 1H).

Workup

  1. temperatureis initially heated to reflux
  2. dissolutionhas dissolved
  3. temperatureis cooled to −75° C
  4. additionis then added
  5. temperatureThe mixture is warmed to rt
  6. stirringstirred for 24 h
  7. extractionextracted with EA
  8. extractionextract
  9. dry with materialis dried over MgSO4
  10. filtrationfiltered
  11. customevaporated
  12. customThe crude product is purified by CC on silica gel eluting with heptane:EA 20:1

Sources & evidence

ORD record
ord-6c4594be88874bd3b3b13a3e63fed423
Source dataset
uspto-grants-2011_10
Patent number
US08044076B2

Reaction notes

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