Methyl 4-Formylbenzoate → Methyl 4-(1-hydroxy-3-methylbutyl)benzoate

HRID 1892642Notes

Reaction equation

HRID 1892642 reaction equation
[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[O:11])=[CH:6][CH:5]=1.[CH2:13]([Mg]Cl)[CH:14]([CH3:16])[CH3:15]>O1CCCC1>[OH:11][CH:10]([C:7]1[CH:8]=[CH:9][C:4]([C:3]([O:2][CH3:1])=[O:12])=[CH:5][CH:6]=1)[CH2:13][CH:14]([CH3:16])[CH3:15]

Participants

4

Reactant 2

HCID 15294Methyl 4-FormylbenzoateHCID 178418368HCID 178418368, compound

Product 1

HCID 59518172Methyl 4-(1-hydroxy-3-methylbutyl)benzoateYield 19%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 4-formyl-benzoic acid methyl ester (1.56 g, 9.50 mmol) in tetrahydrofuran (53 mL) was cooled to 0° C. Isobutylmagnesium chloride (4.75 mL, 2M in THF) was then added dropwise over 15 minutes. The reaction was stirred at 0° C. for 1 hour. The ice bath was removed and the reaction was allowed to warm to room temperature and stir for 1 hour. The reaction was quenched by carefully adding 1N HCl. The reaction was diluted with water and diethylether and the layers were separated. The aqueous was extracted three more times with diethyl ether. The combined organics were dried over magnesium sulfate, filtered, and concentrated. Purification by column chromatography (0-40% ethyl acetate in heptane) gave (+/−)-methyl 4-(1-hydroxy-3-methylbutyl)benzoate (404.6 mg, 19%) as a clear, colorless oil. 1H NMR (400 MHz, CDCl3, δ): 7.99 (d, J=8.2 Hz, 2H), 7.40 (d, J=8.2 Hz, 2H), 4.79 (br. s., 1H), 3.89 (s, 3H), 1.94 (d, J=2.73, 1H), 1.65-1.78 (m, 2H), 1.42-1.52 (m, 1H), 0.91-0.97 (m, 6H).

Workup

  1. customThe ice bath was removed
  2. temperatureto warm to room temperature
  3. stirringstir for 1 hour
  4. customThe reaction was quenched
  5. additionby carefully adding 1N HCl
  6. additionThe reaction was diluted with water and diethylether
  7. customthe layers were separated
  8. extractionThe aqueous was extracted three more times with diethyl ether
  9. dry with materialThe combined organics were dried over magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customPurification by column chromatography (0-40% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-0dd7875bbd0f493fa82e572ae69390a9
Source dataset
uspto-grants-2013_08
Patent number
US08507533B2

Reaction notes

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