Hydrochloric Acid → N-Ethyl 5-chloro-2-(2-methylprop-2-en-1-yloxy)benzylamine

Temperature

65 °C

A mixture of 5-chlorosalicylaldehyde (25.0 g, 0.16 mol), anhydrous potassium carbonate (70.0 g, 0.5 mol), methallyl chloride (27.0 ml, 0.27 mol) and N-methylpyrrolidinone (250 ml) was stirred under reflux condenser at 60-70° C. for 16 hours. The mixture was cooled to 20° C. and treated cautiously with a solution of ethyl amine hydrochloride (40.0 g, 0.49 mol) in 200 ml methanol (frothing occurs). After complete addition the mixture was stirred for 1 hour at 20° C., then treated portionwise with sodium borohydride (4.6 g, 0.12 mol) and small aliquots (~1.0 ml) of ether to reduce frothing. The mixture was stirred for 1 hour at 20° C. and the boron-amine complex decomposed by cautious addition of 6N HCl (200 ml), cooling as necessary. The mixture was Stirred for 1 hour at 20° C., then basified with 2N NaOH to pH10 and extracted with dichloromethane (3×250 ml). The combined organic extracts were washed with water (3×250 ml), dried over anhydrous magnesium sulphate, filtered and evaporated to give a brown oil, which was dissolved in isopropanol (200 ml). Concentrated hydrochloric acid (36% w/v, 10 ml) was added with stirring and the solution cooled at 5° C. for 2 hours, white crystalline needles formed, which were filtered off, washed with isopropanol and ether to give the title compound as the hydrochloride salt (18.0 g, 41%).

1. temperatureThe mixture was cooled to 20° C.
2. additionAfter complete addition the mixture
3. stirringwas stirred for 1 hour at 20° C.
4. stirringThe mixture was stirred for 1 hour at 20° C.
5. temperaturecooling as necessary
6. stirringThe mixture was Stirred for 1 hour at 20° C.
7. extractionextracted with dichloromethane (3×250 ml)
8. washThe combined organic extracts were washed with water (3×250 ml)
9. dry with materialdried over anhydrous magnesium sulphate
10. filtrationfiltered
11. customevaporated
12. customto give a brown oil, which
13. stirringwith stirring
14. temperaturethe solution cooled at 5° C. for 2 hours
15. customwhite crystalline needles formed
16. filtrationwhich were filtered off
17. washwashed with isopropanol and ether

ORD record

ord-61fe56c3f14b4fac8cd9cc64d789063e

Source dataset

uspto-grants-2000_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06100258