Dimethyl Sulfide → (2,6-Dichloro-5-fluoropyridin-3-yl)methanol

To a stirred mixture of 2,6-dichloro-5-fluoro-nicotinic acid (1.0 g, 4.76 mmol) in dry THF (50 mL) under argon was added neat BH3.DMS (1.35 mL, 14.29 mmol) dropwise. The resulting mixture was heated to reflux for 3 hours, cooled to room temperature and quenched by the dropwise addition of water (4 mL). The reaction mixture was concentrated in vacuo. The crude alcohol was diluted with EtOAc, washed with 1N NaOH, 1N HCl, saturated aqueous NaHCO3 solution and brine. The EtOAc layer was dried (MgSO4), filtered and concentrated in vacuo to give 1A (0.93 g, 97%). HPLC Rt=1.79 min (Column: YMC ODS-A 4.6×50 mm (4 min.); Solvent A=10% MeOH, 90% H2O, 0.1% TFA; Solvent B=90% MeOH, 10% H2O, 0.1% TFA); LCMS Found: (M+H)+=210.

1. additionwas added neat BH3
2. temperatureThe resulting mixture was heated
3. temperatureto reflux for 3 hours
4. customquenched by the dropwise addition of water (4 mL)
5. concentrationThe reaction mixture was concentrated in vacuo
6. additionThe crude alcohol was diluted with EtOAc
7. washwashed with 1N NaOH, 1N HCl, saturated aqueous NaHCO3 solution and brine
8. dry with materialThe EtOAc layer was dried (MgSO4)
9. filtrationfiltered
10. concentrationconcentrated in vacuo

ORD record

ord-74b2b48da5274a77b55cc611f83182d3

Source dataset

uspto-grants-2008_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07378426B2