Methanol → Methyl 4-(difluoromethoxy)-3-hydroxybenzoate

温度

52.5 °C

100 g of 3-hydroxy-4-(difluoromethoxy)-benzaldehyde (0.53 mol) were dissolved in MeOH (600 ml), solid Oxone® (325 g, 1.06 mol) was added portion-wise in 1 hour and solution was stirred and warmed to 50-55° C. for 2 hours. The solvent was concentrated under vacuum to 200 ml and water (1 L) was added. The resulting heterogeneous solution was stirred at 50 to 55° C., then toluene (500 ml) was added, and the biphasic mixture vigorously stirred. Aqueous phase was discharged and the organic one was washed with water (500 ml). Active charcoal (10 g) was added and the organic solution stirred for 20 minutes. It was filtered on a celite pad, the solvent was concentrated under vacuum to 2 to 3 volumes, and the obtained solution was warmed to 80 to 90° C. n-Heptane (400 ml) was slowly added. The mixture was cooled to 0° C. and the suspension was stirred at 0° C. over-night. The solid was filtered on a Buchner funnel and washed with n-heptane (100 ml). The obtained white solid was dried under vacuum at room temperature. (yield 70%).

1. concentrationThe solvent was concentrated under vacuum to 200 ml and water (1 L)
2. additionwas added
3. stirringThe resulting heterogeneous solution was stirred at 50 to 55° C.
4. additiontoluene (500 ml) was added
5. stirringthe biphasic mixture vigorously stirred
6. washthe organic one was washed with water (500 ml)
7. additionActive charcoal (10 g) was added
8. stirringthe organic solution stirred for 20 minutes
9. filtrationIt was filtered on a celite pad
10. concentrationthe solvent was concentrated under vacuum to 2 to 3 volumes
11. temperaturethe obtained solution was warmed to 80 to 90° C. n-Heptane (400 ml)
12. additionwas slowly added
13. temperatureThe mixture was cooled to 0° C.
14. stirringthe suspension was stirred at 0° C. over-night
15. filtrationThe solid was filtered on a Buchner funnel
16. washwashed with n-heptane (100 ml)
17. customThe obtained white solid was dried under vacuum at room temperature

ORDレコード

ord-f7c06711277f4a31a07b907e1bbac17c

出典データセット

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09434691B2