Water → HCID 19788163, compound

To a solution of 3-bromomethyl-5-methyl-benzoic acid (3.90 g, 17 mmol) in water (30 mL) and MeCN (30 mL), Cu(NO3)2 hemipentahydrate (12.77 g, 68 mmol) followed by water (50 mL) was added. The turquoise mixture was refluxed for 2 h before it was concentrated to about half of the original volume. The dark green solution was extracted three times with EA (150 mL). The org. extracts were washed twice with water (2×50 mL), combined, dried over Na2SO4, filtered and concentrated. The white residue was separated by prep. HPLC (XBridge Prep C18, 30×75 mm, 5 μm, 95% MeCN in water containing 0.5% of formic acid) to give 3-hydroxymethyl-5-methyl-benzoic acid as a white solid (897 mg; LC-MS*: tR=0.17 min; [M−1]−=164.86), along with the title compound as a white solid (160 mg). To a solution of the above 3-hydroxymethyl-5-methyl-benzoic acid (947 mg, 5.70 mmol) in MeCN (40 mL), MnO2 (1.49 g, 17.1 mmol) was added and the resulting mixture was stirred at 80° C. for 16 h before another portion of MnO2 (1.21 g, 13.9 mmol) and acetonitrile (40 mL) was added and stirring was continued at 80° C. for 4 h. The mixture was filtered over a glass fibre filter, the colourless filtrate was concentrated and purified by prep. HPLC (as above) to give the title compound (504 mg) as a white solid. LC-MS*: tR=0.26 min; [M−1]−=162.88; 1H NMR (D6-DMSO): δ 2.47 (s, 3H), 7.96 (s, 1H), 8.07 (s, 1H), 8.26 (s, 1H), 10.06 (s, 1H), 13.28 (m, 1H).

1. additionwas added
2. concentrationwas concentrated to about half of the original volume
3. extractionThe dark green solution was extracted three times with EA (150 mL)
4. washextracts were washed twice with water (2×50 mL)
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated
8. customThe white residue was separated by prep

ORD record

ord-219c2ab53ada4ab78f91a4227019ef79

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08410151B2