Dimethylamine → 1-(5-Chloro-1H-indol-3-yl)-N,N-dimethylmethanamine

Aqueous dimethylamine (8.0 mL, 63.7 mmol) and aqueous formaldehyde (4.8 mL, 64.0 mL) were combined in dioxane (50 mL) and acetic acid (50 mL). 5-Chloro-1H-indole (9.5 g, 62.5 mmol) in dioxane (30 mL) was added dropwise to the mixture, which was then was stirred at room temperature for 18 hours. The mixture was concentrated to approximately 50 mL by rotary evaporation, diluted with water (≈500 mL), and extracted with ether (~200 mL). The aqueous phase was separated, cooled, made basic with sodium hydroxide, and extracted into methylene chloride. The methylene chloride phase was separated, washed with water and then brine, dried over potassium carbonate, filtered, and evaporated. Crystallization from a mixture of acetone and diisopropyl ether gave 3-(dimethylaminomethyl)-5-chloro-1H-indole (10.6 g, 50.5 mmol) as white crystals, m.p. 148°-150° C.

1. concentrationThe mixture was concentrated to approximately 50 mL by rotary evaporation
2. additiondiluted with water (≈500 mL)
3. extractionextracted with ether (~200 mL)
4. customThe aqueous phase was separated
5. temperaturecooled
6. extractionextracted into methylene chloride
7. customThe methylene chloride phase was separated
8. washwashed with water
9. dry with materialbrine, dried over potassium carbonate
10. filtrationfiltered
11. customevaporated
12. customCrystallization
13. additionfrom a mixture of acetone and diisopropyl ether

ORD record

ord-94fd5603f7e74cfc813e0f42b57d0836

Source dataset

uspto-grants-1995_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05436264