Lithium Hydroxide → 3-Formyl-4-methylbenzoic acid

Under nitrogen, Pd(dppf) (72 mg, 89 μmol) was added to a solution of 3-formyl-4-trifluoromethanesulfonyloxy-benzoic acid methyl ester (2.80 g, 8.97 mmol) in dioxane (40 mL). The mixture was stirred at rt and dimethyl zinc (11.2 g, 13.5 mmol, 12.1 mL of a 1.2M solution in toluene) was added. The mixture was stirred at 75° C. for 1 h. The mixture was cooled to rt before a 2M aq. LiOH solution (40 mL) was added. The mixture was stirred at rt for 2 h before it was concentrated. The residue was dissolved in EA and extracted with 1M aq. NaOH and water. The aq. extracts were acidified by adding 2N aq. HCl (30 mL) and then extracted with EA. The org. extract was dried over Na2SO4, filtered and concentrated. The crude product was purified by prep. HPLC to give the title compound as a pale yellow powder (903 mg). LC-MS*: tR=0.27 min, [M−H]−=162.90; 1H NMR (D6-DMSO): δ 2.69 (s, 3H), 7.49 (d, J=7.8 Hz, 1H), 8.08 (dd, J=7.8, 1.8 Hz, 1H), 8.38 (d, J=1.8 Hz, 1H), 10.29 (s, 1H), 13.20 (s, 1H).

1. stirringThe mixture was stirred at 75° C. for 1 h
2. additionwas added
3. stirringThe mixture was stirred at rt for 2 h before it
4. concentrationwas concentrated
5. dissolutionThe residue was dissolved in EA
6. extractionextracted with 1M aq. NaOH and water
7. additionby adding 2N aq. HCl (30 mL)
8. extractionextracted with EA
9. extractionextract
10. dry with materialwas dried over Na2SO4
11. filtrationfiltered
12. concentrationconcentrated
13. customThe crude product was purified by prep

ORD record

ord-47208e14a804427e8b08c9ff2764adbe

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08410151B2