Dimethylformamide → 2-(Dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridine-3-carbaldehyde

To a solution of 6-bromo-7-(dimethoxymethyl)-1,2,3,4-tetrahydro-1,8-naphthyridine (intermediate 12, 15.0 g, 52.2 mmol) in THF (400 ml) at −78° C. under argon, was added MeLi (1.6 M in Et2O, 32.6 ml, 52.2 mmol), the solution was stirred for 5 min, then n-BuLi (1.6 M in hexane, 35.9 ml, 57.5 mmol) was added slowly and the solution was stirred for 20 min. THF (100 ml) was added to the reaction at −78° C. Subsequently, n-BuLi (1.6 M in hexane, 49.0 ml, 78 mmol) was added and the reaction mixture was stirred for 20 min, then again n-BuLi (1.6 M in hexane, 6.53 ml, 10.45 mmol) was added and the mixture was stirred for 10 min at −78° C. DMF (2.10 ml, 27.2 mmol) was added and the reaction mixture was stirred at −78° C. for 45 min, then it was allowed to warm to room temperature, poured into sat. aq. NH4Cl and extracted twice with DCM. The combined organic phases were dried over Na2SO4, filtered and evaporated to give the title compound as an orange oil. (UPLC-MS 3) tR 0.63 min; ESI-MS 237.2 [M+H]+.

1. stirringthe solution was stirred for 20 min
2. stirringthe reaction mixture was stirred for 20 min
3. stirringthe mixture was stirred for 10 min at −78° C
4. stirringthe reaction mixture was stirred at −78° C. for 45 min
5. extractionextracted twice with DCM
6. dry with materialThe combined organic phases were dried over Na2SO4
7. filtrationfiltered
8. customevaporated

ORD record

ord-1d0f3cfaac4c473b83c4fd5c6bcb4b0a

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09266883B2