Hydrochloric Acid → 1,2,3,4-Tetrahydrobenzo[c]-1,5-naphthyridine

A stirred solution of 1,4-dihydrobenzo[c]-1,5-naphthyridin-2(3H)-one (4.0 g) in sieve dried tetrahydrofuran (400 ml) was treated over a few minutes with 0.98M borane in tetrahydrofuran (62 ml) under a dry nitrogen atmosphere. The resultant suspension was stirred for 5 hours at ambient temperature during which time a solution formed. After standing overnight at ambient temperature the solution was treated with glacial acetic acid (16 ml) followed by stirring for several minutes. The solution was then treated with 10% sodium hydroxide solution (180 ml) to give a biphasic system. Concentration on a rotary evaporator to remove the tetrahydrofuan gave a suspension of a solid which was extracted with CH2Cl2 (2×800 ml). The combined, dried (Na2SO4) organic phase was concentrated to afford a solid (5.18 g, tentatively identified as a borane complex). A suspension of the solid in glacial acetic acid (15 ml) was treated gradually with concentrated HCl (50 ml). When the gas evolution ceased, the mixture was warmed for a few minutes and then stirred for 0.5 hour at ambient temperature. The solution was strained through glass wool, and the filtrate was diluted with ice (300 ml) and water (100 ml) and then made alkaline with 50% sodium hydroxide solution. The mixture was extracted with CH2Cl2, dried (Na2SO4), filtered and concentrated to dryness (3.7 g). Recrystallization from acetonitrile (20 ml) gave 1.97 g of a crystalline material which was combined with 2.01 g of a similarly prepared product. The material was purified by HPLC (silica gel, eluted with 5% methanol in ethyl acetate) to give 3.72 g of a solid. Recrystallization from acetonitrile (20 ml) afforded 3.01 g of crystals, m.p. 124.5°-127.5° C.

1. customformed
2. customto give a biphasic system
3. concentrationConcentration
4. customon a rotary evaporator
5. customto remove the tetrahydrofuan
6. customgave
7. additiona suspension of a solid which
8. extractionwas extracted with CH2Cl2 (2×800 ml)
9. dry with materialdried (Na2SO4) organic phase
10. concentrationwas concentrated
11. customto afford a solid (5.18 g
12. temperaturethe mixture was warmed for a few minutes
13. stirringstirred for 0.5 hour at ambient temperature
14. extractionThe mixture was extracted with CH2Cl2
15. dry with materialdried (Na2SO4)
16. filtrationfiltered
17. concentrationconcentrated to dryness (3.7 g)
18. customRecrystallization from acetonitrile (20 ml)

ORD record

ord-92ed663bcafe45089a93cb6d5b957943

Source dataset

uspto-grants-1987_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04652567