Dimethylformamide → Ethyl 2-methyl-4-vinylbenzoate

HRID 587189Notes

Reaction equation

HRID 587189 reaction equation
[CH:1]([C:3]1[CH:11]=[CH:10][C:6]([C:7]([OH:9])=[O:8])=[C:5]([CH3:12])[CH:4]=1)=O.Br[C:14]1C=CC(C(O)=O)=C(C)[CH:15]=1.[Li][CH2:25]CCC.CN(C=O)C>C1COCC1>[CH3:12][C:5]1[CH:4]=[C:3]([CH:1]=[CH2:25])[CH:11]=[CH:10][C:6]=1[C:7]([O:9][CH2:14][CH3:15])=[O:8]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 995704-Bromo-2-methylbenzoic acidHCID 207748714-Formyl-2-methylbenzoic acidHCID 178418339Butyllithium

Product 1

HCID 58390837Ethyl 2-methyl-4-vinylbenzoateYield 40%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

4-Formyl-2-methylbenzoic acid (AI15). To a stirred solution of 4-bromo-2-methylbenzoic acid (10 g, 46.4 mmol) in dry THF (360 mL) at −78° C. was added n-BuLi (1.6 M solution in hexanes; 58.17 mL, 93.0 mmol) and DMF (8 mL). The reaction mixture was stirred at −78° C. for 1 h then was warmed to 25° C. and stirred for 1 h. The reaction mixture was quenched with 1 N HCl solution and extracted with EtOAc. The combined EtOAc extracts were washed with brine and dried over Na2SO4 and concentrated under reduced pressure. The residue was washed with n-hexane to afford the title compound as a solid (3.0 g, 40%): mp 196-198° C.; 1H NMR (400 MHz, DMSO-d6) δ 13.32 (br s, 1H), 10.05 (s, 1H), 7.98 (m, 1H), 7.84 (m, 2H), 2.61 (s, 3H); ESIMS m/z 163.00 ([M−H]−).

Workup

  1. temperaturethen was warmed to 25° C.
  2. stirringstirred for 1 h
  3. customThe reaction mixture was quenched with 1 N HCl solution
  4. extractionextracted with EtOAc
  5. washThe combined EtOAc extracts were washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated under reduced pressure
  8. washThe residue was washed with n-hexane

Sources & evidence

ORD record
ord-fdc44969848f4889ac9a7ad2d642511b
Source dataset
uspto-grants-2016_01
Patent number
US09226500B2

Reaction notes

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