2-Methoxyethylamine → 6-Bromo-N-(2-methoxyethyl)-3-pyridinemethanamine

To a solution of 6-bromonicotinaldehyde (7) (5 g, 26.9 mmol) in DCM (40 mL) was added 2-methoxyethylamine (8) (2.80 mL, 32.3 mmol). After 10 min, sodium triacetoxyborohydride (7.98 g, 37.6 mmol) was added to the mixture and the mixture was stirred at r.t. for 17 h. Additional amounts of DCM (100 mL), water (50 mL) and NH4Cl (50 mL) were added to the reaction mixture, which turned into a biphasic system. The organic phase was collected and the aqueous layer was extracted with DCM (3×100 mL). The combined organic solution were washed with brine, dried over anhydrous MgSO4 and concentrated under reduce pressure. The residue was purified by flash column chromatography (eluent a gradient DCM/MeOH from 98/2 to 95/5), to afford intermediate 9 (2.958 g, 45% yield) as a brown oil. MS (m/z): 245.1 (M+H). 1H NMR (400 MHz, DMSO-d6) δ (ppm): 8.31 (dd, J=2.6, 0.6 Hz, 1H), 7.70 (dd, J=8.2, 2.6 Hz, 1H), 7.58 (d, J=8.4 Hz, 1H), 3.69 (s, 2H), 3.37 (t, J=5.8 Hz, 2H), 3.22 (s, 3H), 2.60 (t, J=5.8 Hz, 2H).

1. customThe organic phase was collected
2. extractionthe aqueous layer was extracted with DCM (3×100 mL)
3. washThe combined organic solution were washed with brine
4. dry with materialdried over anhydrous MgSO4
5. concentrationconcentrated
6. customThe residue was purified by flash column chromatography (eluent a gradient DCM/MeOH from 98/2 to 95/5),

ORD record

ord-131fc46c9918473c8d19912060fea193

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09018378B2