Sodium borohydride → 6-Hydroxymethyl-nicotinic acid methyl ester

Temperature

-78 °C

Diisobutylaluminum hydride (1.5 M solution in toluene, 9.82 mL) was added dropwise to a solution of 6-(methoxy-methyl-carbamoyl)-nicotinic acid methyl ester (1.1 g, 4.91 mmol) in THF (50 mL) at −78° C. over 10 minutes. The reaction mixture was stirred for 2 hours at −78° C., quenched with 5% HCl/ethanol and warmed to room temperature. The reaction mixture was concentrated in vacuo and the resulting residue was taken up in saturated K2CO3 and extracted with ethyl acetate (2×). The combined organic extracts were washed with brine, dried (Na2SO4), filtered and concentrated in vacuo. MeOH (15.0 mL) was added to the crude reaction mixture and cooled to 0° C. Sodium borohydride (0.280 g, 7.20 mmol) was added in two portions to the reaction mixture and stirred at 0° C. for 30 minutes. Additional sodium borohydride (0.136 g, 3.6 mmol) was added to the reaction mixture, warmed to room temperature and stirred for 2 hours. The reaction mixture was diluted with dichloromethane (75.0 mL), washed with water and saturated NaHCO3, dried (Na2SO4), filtered and evaporated to yield 6-hydroxymethyl-nicotinic acid methyl ester (0.400 g, 49% yield) as a solid.

1. customquenched with 5% HCl/ethanol
2. temperaturewarmed to room temperature
3. concentrationThe reaction mixture was concentrated in vacuo
4. extractionextracted with ethyl acetate (2×)
5. washThe combined organic extracts were washed with brine
6. dry with materialdried (Na2SO4)
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. additionMeOH (15.0 mL) was added to the crude
10. customreaction mixture
11. temperaturecooled to 0° C
12. stirringstirred at 0° C. for 30 minutes
13. temperaturewarmed to room temperature
14. stirringstirred for 2 hours
15. washwashed with water and saturated NaHCO3
16. dry with materialdried (Na2SO4)
17. filtrationfiltered
18. customevaporated

ORD record

ord-9ec15917f51e45bca8bb4bc810f1f615

Source dataset

uspto-grants-2010_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07671043B2