Dimethylamine → Dapoxetine

Temperature

-2.5 °C

50 gms of 1-phenyl,3-napthyloxy 1-propanol, 375 ml of tetrahydrofuran (THF)), 5 mg of dimethylamino pyridine (DMAP) and 60 ml of triethyl amine) were charged in a clean and dry R.B. flask. The reaction mixture was cooled to −5 to 0° C. and a mixture of methane sulfonyl chloride (33 gm) and tetrahydrofuran (125 ml) was added. The resultant reaction mixture was stirred at about 0 to 5° C. for 6 hours and then dimethylamine gas was passed into the reaction mass. The temperature of the reaction mass was raised to room temperature and stirred for about 40 hours. After the completion of the reaction as determined by TLC, the reaction mass was quenched by pouring into chilled water (500 ml) slowly and the pH was adjusted to 0.5 to 1 with concentrated hydrochloric acid. 250 ml of toluene (250 ml) was added and stirred for 30 minutes. The layers were separated and the aqueous layer pH was adjusted to 9 to 10 with 5% w/v sodium hydroxide solution. The aqueous layer extracted with methylene dichloride (4×300 ml) and the solvent distilled off completely to obtain a residue. 100 ml of Ethyl acetate was added to the residue obtained and the mixture was stirred for about 30 minutes, filtered through celite and washed with ethyl acetate. The filtrate was distilled off completely to obtain 47 gm of racemic dapoxetine as a residual oil.

1. customdry R.B
2. additiona mixture of methane sulfonyl chloride (33 gm) and tetrahydrofuran (125 ml)
3. additionwas added
4. customThe resultant reaction mixture
5. temperatureThe temperature of the reaction mass was raised to room temperature
6. stirringstirred for about 40 hours
7. customAfter the completion of the reaction
8. customthe reaction mass was quenched
9. additionby pouring
10. temperatureinto chilled water (500 ml) slowly
11. addition250 ml of toluene (250 ml) was added
12. stirringstirred for 30 minutes
13. customThe layers were separated
14. extractionThe aqueous layer extracted with methylene dichloride (4×300 ml)
15. distillationthe solvent distilled off completely
16. customto obtain a residue
17. customobtained
18. stirringthe mixture was stirred for about 30 minutes
19. filtrationfiltered through celite
20. washwashed with ethyl acetate
21. distillationThe filtrate was distilled off completely

ORD record

ord-8a4a3d090d3a4885ae9ca877c82dd58b

Source dataset

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08546615B2