4-Methylmorpholine → 2-(4-formylphenyl)acetic Acid

To a stirred solution of the title compound of Example 1 (46.9 g, 200 mmol) in dioxane (500 mL) and water (500 mL) was added osmium tetroxide (0.5 g, 4% in water), followed by sodium periodate (85.56 g, 400 mmol). The reaction mixture was monitored by HPLC, stirred for 1 hour and N-methylmorpholine (1.0 g) was added, followed by additional osmium tetroxide (1.0 g) after another 16 hours. After 4 hours stirring at room temperature, additional sodium periodate (40 g) was added, the reaction stirred for 21 hours, filtered, and the filter cake washed with ethyl acetate (500 mL). The phases were separated, the aqueous layer extracted with ethyl acetate (500 mL), the remaining aqueous layer acidified with hydrochloric acid (30 mL), extracted with ethyl acetate (500 mL), and the combined organic phases washed with water (500 mL), saturated sodium chloride solution (250 mL), dried over sodium sulfate, filtered and the solvent removed in vacuo. The wet solid was triturated with methyl tert-butyl ether (50 mL) and to the resulting slurry was added pentane (100 mL). The slurry was filtered, the solid product was washed with pentane (2×25 mL) and dried to give the title compound (12.4 g, 38%). HPLC: 2.19 min (YMC S5 ODS column 4.6×50 mm, 10-90% aqueous methanol over 4 minutes containing 0.2% phosphoric acid, 4 mL/min, monitoring at 220 nm). 1H NMR (d6-DMSO): δ 9.99 (s, 1H), 7.85-7.87 (d, 2H), 7.49-7.51 (d, 2H); 3.72 (s, 3H).

1. stirringAfter 4 hours stirring at room temperature
2. stirringthe reaction stirred for 21 hours
3. filtrationfiltered
4. washthe filter cake washed with ethyl acetate (500 mL)
5. customThe phases were separated
6. extractionthe aqueous layer extracted with ethyl acetate (500 mL)
7. extractionextracted with ethyl acetate (500 mL)
8. washthe combined organic phases washed with water (500 mL), saturated sodium chloride solution (250 mL)
9. dry with materialdried over sodium sulfate
10. filtrationfiltered
11. customthe solvent removed in vacuo
12. customThe wet solid was triturated with methyl tert-butyl ether (50 mL) and to the resulting slurry
13. additionwas added pentane (100 mL)
14. filtrationThe slurry was filtered
15. washthe solid product was washed with pentane (2×25 mL)
16. customdried

ORD 기록

ord-7b22710c983e412e9cb3cdde9c286264

출처 데이터셋

uspto-grants-2003_09

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US06613911B2