反应详情

A stirred solution of 1-(phenylacetyl)-1,2,3,4-tetrahydrobenzo[c]-1,5-naphthyridine (5.11 g) in sieve dried tetrahydrofuran (300 ml) was treated rapidly with 1M borane in tetrahydrofuran (68 ml). The resultant solution was stirred overnight under a nitrogen atmosphere with exclusion of moisture and thereafer allowed to stand 24 hours. The reaction was quenched by dropwise addition of 10% sodium hydroxide solution (60 ml) and then concentrated to remove the tetrahydrofuran. The oil-aqueous phase mixture was further diluted with water (100 ml) and extracted with dichloromethane (2×200 ml). The combined and dried (Na2SO4) organic phase was filtered and concentrated to a viscous oil (a borane complex of the product). A solution of the oil in glacial acetic acid (30 ml) was cautiously treated with concentrated hydrochloric acid (15 ml) under nitrogen (vigorous gas evolution noted). After stirring for 1 hour at ambient temperature the solution was decanted over crushed ice (500 ml), diluted with water (200 ml) and basified with 50% sodium hydroxide solution. The mixture was extracted with CH2Cl2 (2×250 ml) and the combined and dried (Na2SO4) organic phase was filtered and concentrated to an oil (4.72 g). A TLC analysis (silica gel, ethyl acetate) indicated the oil was a mixture of the desired product and 1,2,3,4-tetrahydrobenzo[c]-1,5-naphthyridine. The mixture was separated by preparative HPLC (silica gel, eluted with ethyl acetate, overlap fractions repurified using new columns) to give 1.92 g of the product as a viscous oil which was combined with a similarly prepared material to give 2.52 g of pure product.

1. customThe reaction was quenched by dropwise addition of 10% sodium hydroxide solution (60 ml)
2. concentrationconcentrated
3. customto remove the tetrahydrofuran
4. additionThe oil-aqueous phase mixture was further diluted with water (100 ml)
5. extractionextracted with dichloromethane (2×200 ml)
6. dry with materialdried (Na2SO4) organic phase
7. filtrationwas filtered
8. concentrationconcentrated to a viscous oil (a borane complex of the product)
9. additionA solution of the oil in glacial acetic acid (30 ml) was cautiously treated with concentrated hydrochloric acid (15 ml) under nitrogen (vigorous gas evolution noted)
10. customwas decanted
11. customover crushed ice (500 ml)
12. additiondiluted with water (200 ml)
13. extractionThe mixture was extracted with CH2Cl2 (2×250 ml)
14. dry with materialdried (Na2SO4) organic phase
15. filtrationwas filtered
16. concentrationconcentrated to an oil (4.72 g)
17. additiona mixture of the desired product and 1,2,3,4-tetrahydrobenzo[c]-1,5-naphthyridine
18. customThe mixture was separated by preparative HPLC (silica gel, eluted with ethyl acetate, overlap fractions repurified using new columns)