Hydrochloric Acid → (S)-7-Nitro-1,5,10,10a-tetrahydrothiazolo[3,4-b]isoquinoline-3-thione

Temperature

20 °C

Finely powdered anhydrous sodium nitrate (85 g.) is added to a solution of (S)-3-hydroxysulphonyloxymethyl1,2,3,4-tetrahydroisoquinoline (122 g.) in trifluoroacetic acid (1,000 cc.). The reaction mixture is stirred for 5 days at a temperature of about 20° C. and is then evaporated under reduced pressure (25 mm. Hg, followed by 1 mm. Hg). The residue is washed with diethyl ether (3 × 200 cc.). The light yellow solid obtained is ground and then dried at 40° C. under reduced pressure (1 mm.Hg). The solid thus obtained is dissolved in 0.3N sodium hydroxide solution (5,000 cc.); carbon disulphide (35 cc.) is added to the solution obtained, whilst stirring, and the stirring is continued at a temperature of about 20° C. for 17 hours. The mixture is neutralised by adding 4N hydrochloric acid. The precipitate formed is filtered off, washed copiously with water and then with ethanol, dried under reduced pressure (0.1 mm. Hg) and then dissolved in boiling toluene (3,200 cc.). The insoluble matter is filtered off over Celite and the filtrate is cooled to about 10° C. The crystals which have appeared are filtered off, washed with ethanol (100 cc.), dried at 80° C. under reduced pressure (0.1 mm. Hg) and recrystallised from a mixture of acetonitrile and ethanol (1:1 by volume) (1,000 cc.). (S)-7-Nitro-1,5,10,10a-tetrahydrothiazolo[3,4-b]isoquinoline-3-thione (45 g.) melting at 182° C., is obtained.

1. customis then evaporated under reduced pressure (25 mm. Hg, followed by 1 mm. Hg)
2. washThe residue is washed with diethyl ether (3 × 200 cc.)
3. customThe light yellow solid obtained
4. customdried at 40° C. under reduced pressure (1 mm.Hg)
5. customThe solid thus obtained
6. customobtained
7. stirringwhilst stirring
8. waitthe stirring is continued at a temperature of about 20° C. for 17 hours
9. customThe precipitate formed
10. filtrationis filtered off
11. washwashed copiously with water
12. dry with materialwith ethanol, dried under reduced pressure (0.1 mm. Hg)
13. dissolutiondissolved
14. filtrationThe insoluble matter is filtered off over Celite
15. temperaturethe filtrate is cooled to about 10° C
16. filtrationThe crystals which have appeared are filtered off
17. washwashed with ethanol (100 cc.)
18. customdried at 80° C. under reduced pressure (0.1 mm. Hg)
19. customrecrystallised from a mixture of acetonitrile and ethanol (1:1 by volume) (1,000 cc.)

ORD record

ord-01b90c607e0f424ebec590362fad1f71

Source dataset

uspto-grants-1977_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04064247