Benzoyl chloride → N-[(3,4-dimethoxyphenyl)methyl]benzamide

Temperatur

15 °C

To a mixture of 3,4-dimethoxybenzylamine (24.0 g, 0.144 mol), tetrahydrofuran (192 mL) and triethylamine (15.5 g, 0.153 mol) was added dropwise benzoyl chloride (20.7 g, 0.147 mol) at −7-0° C. During addition dropwise, tetrahydrofuran (24 mL) was added thereto to stir the mixture. After adding dropwise, the dropping funnel was washed with tetrahydrofuran (12 mL), and tetrahydrofuran (24 mL) was added again thereto. The reaction mixture was gradually warmed to about 15° C. The reaction was monitored by TLC (eluent: hexane/ethyl acetate (1:1)). To the reaction mixture was added water (48 mL) at 5-8° C., and then added ethyl acetate (144 mL). The organic layer was separated, and the aqueous layer was extracted with ethyl acetate (48 mL×2). The combined organic layers were washed successively with 10% hydrochloric acid (48 mL), saturated aqueous sodium hydrogen carbonate solution (48 mL), water (48 mL) and saturated brine (48 mL), and dried over magnesium sulfate (12 g), and the solvent was evaporated under reduced pressure at 40° C. or lower. To the concentrate (40 g) was added ethyl acetate (89 g), and the mixture was homogenized with warming at 50° C., and cooled to 11° C. The solid was collected by filtration, washed with cold ethyl acetate (15 mL), and dried under reduced pressure at 40° C. or lower to give N-benzoyl-3,4-dimethoxybenzylamine (33.3 g, 85.4%) as white crystals.

1. additionDuring addition dropwise
2. additionAfter adding dropwise
3. washthe dropping funnel was washed with tetrahydrofuran (12 mL), and tetrahydrofuran (24 mL)
4. additionwas added again
5. additionTo the reaction mixture was added water (48 mL) at 5-8° C.
6. customThe organic layer was separated
7. extractionthe aqueous layer was extracted with ethyl acetate (48 mL×2)
8. washThe combined organic layers were washed successively with 10% hydrochloric acid (48 mL), saturated aqueous sodium hydrogen carbonate solution (48 mL), water (48 mL) and saturated brine (48 mL)
9. dry with materialdried over magnesium sulfate (12 g)
10. customthe solvent was evaporated under reduced pressure at 40° C.
11. concentrationTo the concentrate (40 g)
12. additionwas added ethyl acetate (89 g)
13. stirringthe mixture was homogenized
14. temperaturewith warming at 50° C.
15. temperaturecooled to 11° C
16. filtrationThe solid was collected by filtration
17. washwashed with cold ethyl acetate (15 mL)
18. customdried under reduced pressure at 40° C.

ORD-Eintrag

ord-64ad7fa6484a49c2b6241846d4d053c2

Quelldatensatz

uspto-grants-2013_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08530506B2