Dimethylformamide → 2-Ethyl-5-formyl-4-methylbenzoic acid

HRID 541338Notes

Reaction equation

[CH2:1]([C:3]1[CH:11]=[C:10]([CH3:12])[C:9](I)=[CH:8][C:4]=1[C:5]([OH:7])=[O:6])[CH3:2].[Li]CCCC.CN([CH:22]=[O:23])C>O1CCCC1>[CH2:1]([C:3]1[CH:11]=[C:10]([CH3:12])[C:9]([CH:22]=[O:23])=[CH:8][C:4]=1[C:5]([OH:7])=[O:6])[CH3:2]

Participants

Conditions

Temperature: 25 °C

Procedure

To a stirred solution of 2-ethyl-5-iodo-4-methylbenzoic acid (compound 211.3, 5.00 g, 17.2 mmol, 1.00 equiv) in tetrahydrofuran (100 mL) at −78° C. under nitrogen was added dropwise n-BuLi (17 mL, 2 M in THF, 2.00 equiv). After 1 h at −78° C., DMF (7.00 g, 95.8 mmol, 3.00 equiv) was added dropwise at −78° C. The resulting solution was slowly warmed up to 25° C., then carefully quenched with water followed by the addition of 10 mL of HCl (aq., 6 M). The aqueous phase was extracted with 3×100 mL of ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified using silica gel column chromatography with ethyl acetate/petroleum ether (2:1) as eluent to furnish 450 mg (14%) of 2-ethyl-5-formyl-4-methylbenzoic acid as a yellow solid.

Workup

customcarefully quenched with water
additionfollowed by the addition of 10 mL of HCl (aq., 6 M)
extractionThe aqueous phase was extracted with 3×100 mL of ethyl acetate
dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
concentrationconcentrated in vacuo
customThe residue was purified

Sources & evidence

ORD record: ord-385e6b342e004975a7ec32bea2d1e733
Source dataset: uspto-grants-2014_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08871790B2

Reaction notes

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