[CH:1]1([C:5]2[C:13](I)=[CH:12][C:8]([C:9]([OH:11])=[O:10])=[C:7]([CH3:15])[CH:6]=2)[CH2:4][CH2:3][CH2:2]1.[O:16]1CCC[CH2:17]1.C([Li])CCC.CN(C)C=O>CCOCC>[CH:1]1([C:5]2[C:13]([CH:17]=[O:16])=[CH:12][C:8]([C:9]([OH:11])=[O:10])=[C:7]([CH3:15])[CH:6]=2)[CH2:4][CH2:3][CH2:2]1Into a three neck round-bottom flask, which was purged and maintained with an inert atmosphere of nitrogen, was placed a solution of 4-cyclobutyl-5-iodo-2-methylbenzoic acid (compound 230.1, 5.00 g, 12.7 mmol, 1.00 equiv, 80%) in a solvent mixture of tetrahydrofuran and Et2O (50/50 mL). This was followed by the addition of butyllithium (15 mL, 2.50 equiv, 95%) dropwise with stirring at −78° C. To this was added N,N-dimethylformamide (2.50 g, 32.5 mmol, 2.00 equiv). The resulting solution was stirred for 1 h at −78° C. and then carefully quenched by slow addition of 50 mL of NH4Cl (aq.). The pH was adjusted to 1-2 with hydrogen chloride (6 M). The resulting solution was diluted with 100 mL of ethyl acetate, then washed with 4×50 mL of brine. The organic layer was dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified using silica gel column chromatography with ethyl acetate/petroleum ether (1:1) as eluent to furnish 1.62 g (41%) of 4-cyclobutyl-5-formyl-2-methylbenzoic acid as a white solid.
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