Methanol → 3-(Cyclopropylmethoxy)-4-(difluoromethoxy)benzoic acid methyl ester

温度

57.5 °C

873 g of 3-(cyclopropylmethoxy)-4-(difluoromethoxy)-benzaldehyde (3.61 mol) were dissolved in MeOH (4.4 L), then solid Oxone® (1.86 Kg, 6.06 mol) was added portion-wise in 1 hour, and the solution was stirred and warmed to 55 to 60° C. for 2 hours. The solvent was concentrated under vacuum to 1.6 L and water (7 L) was added. The resulting heterogeneous solution was stirred at 50 to 55° C., then toluene (3 L) was added, and the biphasic mixture vigorously stirred. Aqueous phase was discharged and the organic one was washed with water (3 L). The solvent was concentrated under vacuum to 2 to 3 volumes, and the obtained solution warmed to 80 to 90° C. n-Heptane (5.5 L) was slowly added. The mixture was cooled to −10° C., and the suspension was stirred at −10° C. over-night. The solid was filtered on a Buchner funnel and washed with n-heptane (1 L). The obtained yellow solid was dried under vacuum at room temperature. (yield 52%).

1. concentrationThe solvent was concentrated under vacuum to 1.6 L and water (7 L)
2. additionwas added
3. stirringThe resulting heterogeneous solution was stirred at 50 to 55° C.
4. additiontoluene (3 L) was added
5. stirringthe biphasic mixture vigorously stirred
6. washthe organic one was washed with water (3 L)
7. concentrationThe solvent was concentrated under vacuum to 2 to 3 volumes
8. temperaturethe obtained solution warmed to 80 to 90° C. n-Heptane (5.5 L)
9. additionwas slowly added
10. temperatureThe mixture was cooled to −10° C.
11. stirringthe suspension was stirred at −10° C. over-night
12. filtrationThe solid was filtered on a Buchner funnel
13. washwashed with n-heptane (1 L)
14. customThe obtained yellow solid was dried under vacuum at room temperature

ORDレコード

ord-c1d41047786a48178e676e36ef809d32

出典データセット

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09434691B2