Trimethyl orthoformate → 4-bromo-N-methylpyridin-3-amine

Temperature

0 °C

A mixture of 4-bromo-pyridin-3-ylamine (2 g, 11.56 mmol, CAS RN 239137-39-4) in trimethyl orthoformate (19 mL, 173.4 mmol, CAS RN 149-73-5) and a catalytic amount of TFA (1 drop) was heated to reflux for 2 hours. Volatiles were removed in vacuo, the resultant dark brown material was dissolved in THF (40 mL), treated portionwise with LiAlH4 (440 mg, 11.56 mmol) at 0° C. and then left stirring at 0° C. for 30 minutes. The reaction mixture was quenched with saturated aqueous NH4Cl solution (15 mL), filtered through a bed of celite, and the residue further washed with EtOAc (30 mL). The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and evaporated off in vacuo. The residue was purified by column chromatography over alumina (10% EtOAc in n-hexane) to afford the title compound. Light yellow oil (875 mg, 40%). MS (ESI): m/z=187.2 [M+H]+.

1. temperatureto reflux for 2 hours
2. customVolatiles were removed in vacuo
3. dissolutionthe resultant dark brown material was dissolved in THF (40 mL)
4. waitleft
5. customThe reaction mixture was quenched with saturated aqueous NH4Cl solution (15 mL)
6. filtrationfiltered through a bed of celite
7. washthe residue further washed with EtOAc (30 mL)
8. washThe combined organic layers were washed with brine
9. dry with materialdried over anhydrous Na2SO4
10. filtrationfiltered
11. customevaporated off in vacuo
12. customThe residue was purified by column chromatography over alumina (10% EtOAc in n-hexane)

ORD record

ord-e72eb2af863b418db72c0aa513d4cbcc

Source dataset

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08987307B2