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

Participants

Reaction Conditions

Reaction Steps

In a 22 L reactor methyl-4-formylbenzoate (500 g) is dissolved in THF (5 L). The solution is cooled to −40° C., and isobutylmagnesium bromide (2.0 M in Et2O, 1.67 L) is added by addition funnel, maintaining the internal temperature less than −20° C. The reaction is followed by HPLC and when the amount of methyl-4-formylbenzoate is found to be less than 1%, the reaction is quenched with MeOH (148 mL) while maintaining the internal temp below 2° C. The reaction is charged with 5 M HCl (700 mL) while maintaining the internal temp below 10° C. Transfer the resultant biphasic mixture to a 12 L With bottom valve, rinsing with 300 mL of heptane. The resulting layers are separated and the organic layer is washed with 1 M HCl (500 mL). The aqueous layers are combined and extracted with tert-butyl methyl ether (500 mL). The combined organic extracts are concentrated in vacuo. The resulting residue is diluted with heptane (800 mL) and concentrated in vacuo to dry the material azeotropically. The resulting oil is purified by silica gel chromatography to give 246.3 g (37%) of the desired carbinol as a yellow oil that solidifies on standing in the refrigerator to a white waxy solid. 1H NMR (500 MHz, CDCl3): δ 8.0 (d, 2H), 7.4 (d, 2H), 4.8 (dd, 1H), 3.9 (s, 3H), 1.85 (s, 1H), 1.71 (m, 2H), 1.48 (m, 1H), 0.95 (d, 6H).

Provenance & Evidence