Methyl Ethyl Ketone → 6-Bromo-3-pyridinemethanol

To a mechanically-stirred solution of 80 g of methyl 6-bromo-nicotinate in a mixture of 386 mL of tetrahydrofuran and 114 mL of toluene at 0° C. was added drop by drop a 1.5 molar toluene solution of diisobutyl aluminium hydride at a rate such that the temperature never exceeded 10° C. This addition took 50 minutes. 21.59 mL of methyl ethyl ketone was added to the reaction mixture while the temperature rose to 25° C. A solution of 2.58 g of NaOH in 40 mL of water was added to the reaction mixture drop by drop (CAUTION: EXOTHERMIC). 121 mL of water was added with vigorous stirring. After completion of the addition, a white solid appeared. The mixture was filtered through celite and 196 mL of toluene was used to wash the solid and filter. The filtrate was concentrated in vacuo and 48 mL of heptane was added. The mixture was cooled in an ice-salt bath for 1 hour. The precipitated solid was filtered and washed with heptane to give 62.09 g of 3-hydroxymethyl-6-bromopyridine as a solid.

1. additionThis addition
2. customrose to 25° C
3. additionAfter completion of the addition
4. filtrationThe mixture was filtered through celite and 196 mL of toluene
5. washto wash the solid
6. filtrationfilter
7. concentrationThe filtrate was concentrated in vacuo and 48 mL of heptane
8. additionwas added
9. temperatureThe mixture was cooled in an ice-salt bath for 1 hour
10. filtrationThe precipitated solid was filtered
11. washwashed with heptane

ORD record

ord-c2b8b28ff16f4240bad50857a6e99962

Source dataset

uspto-grants-1995_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05420270