Sodium Hydroxide → (6-Methoxypyridin-3-yl)methanol

To a solution of methyl-6-methoxynicotinate (1) (650 g, 3.89 mol) in t-butyl methyl ether (hereinafter abbreviated as “MTBE”) (6.5 L) cooled in an ice bath was added sodium bis(2-methoxyethoxy)aluminum hydride (65% solution in toluene, 1.45 kg, 4.67 mol) under a nitrogen atmosphere over a period of 1.3 hours. After stirring for 20 minutes, a 3.5 N aqueous solution of sodium hydroxide (2.6 L) was added to the reaction mixture while keeping the temperature 15° C. or below. The reaction mixture was stirred at 32° C. for 45 minutes and then the organic layer was separated and the aqueous layer was re-extracted with MTBE (2.3 L). The organic layers were combined and concentrated under reduced pressure to dryness, and then toluene (1.3 L) was added to the residue and azeotropic distillation was carried out. Azeotropic distillation with toluene (1.3 L) was repeated three times to give 597 g of the title compound as a pale yellow oil (yield 100%).

1. temperaturecooled in an ice bath
2. customthe temperature 15° C. or below
3. stirringThe reaction mixture was stirred at 32° C. for 45 minutes
4. customthe organic layer was separated
5. extractionthe aqueous layer was re-extracted with MTBE (2.3 L)
6. concentrationconcentrated under reduced pressure to dryness
7. additiontoluene (1.3 L) was added to the residue and azeotropic distillation
8. distillationAzeotropic distillation with toluene (1.3 L)

ORD record

ord-f645269f1839432a904f201089de7e9c

Source dataset

uspto-grants-2008_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07396928B2