Thionyl Chloride → 3-(chloromethyl)-N-methylbenzamide

To a solution of 3-(chloromethyl)-benzoic acid (34.1 g, 200 mmol) in toluene (125 mL) was added thionyl chloride (21.9 mL, 300 mmol) at room temperature. The resulting solution was heated at reflux for 15 hours. The reaction mixture was cooled to room temperature and concentrated under vacuum. The resulting oily residue was azeotroped with toluene and dried under high vacuum to obtain the crude acid chloride. To a suspension of the above crude acid chloride (200 mmol) in dichloromethane (400 mL) was added methylamine hydrochloride (14.9 g, 220 mmol) at −5° C. to 0° C. Diisopropylethylamine (69.6 mL, 400 mmol) was added drop-wise over 15-20 minutes at 0° C. After completion of the addition, the mixture was stirred for 45 minutes at 0° C., then warmed to room temperature. After stirring at room temperature for 15 minutes, the reaction mixture was diluted with water (300 mL) and the aqueous layer was extracted with dichloromethane (100 mL). The combined organic layers were washed with brine and dried over anhydrous magnesium sulfate. Filtration and concentration gave the crude solid which was dissolved in toluene at ˜60-70° C. The resulting solution was stored in the refrigerator overnight and the precipitated solids were collected by filtration and then washed with hexanes. After drying in air, 3-(chloromethyl)-N-methyl-benzamide (80%) was isolated as a light yellow solid.

1. temperatureThe resulting solution was heated
2. temperatureat reflux for 15 hours
3. concentrationconcentrated under vacuum
4. customThe resulting oily residue was azeotroped with toluene
5. customdried under high vacuum
6. customto obtain the crude acid chloride
7. additionAfter completion of the addition
8. temperaturewarmed to room temperature
9. stirringAfter stirring at room temperature for 15 minutes
10. extractionthe aqueous layer was extracted with dichloromethane (100 mL)
11. washThe combined organic layers were washed with brine
12. dry with materialdried over anhydrous magnesium sulfate
13. filtrationFiltration and concentration
14. customgave the crude solid which
15. customwas stored in the refrigerator overnight
16. filtrationthe precipitated solids were collected by filtration
17. washwashed with hexanes
18. customAfter drying in air

ORD record

ord-23fc8bff6e4f477b938c1db69d4ea9bb

Source dataset

uspto-grants-2012_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08124629B2