Preparation and application of (R)-2-(1-hydroxyethyl)pyridine_Industrial additives

Background and overview of preparation and application of (R)-2-(1-hydroxyethyl)pyridine

(R)-2-(1-hydroxyethyl)pyridine is an organic intermediate that can be prepared from (±)-1-(pyridin-2-yl)-ethanol in two steps. There are reports in the literature that it can be used to prepare bromodomain inhibitors.

Preparation and application of (R)-2-(1-hydroxyethyl)pyridine

Preparation and Application of (R)-2-(1-hydroxyethyl)pyridine Step 1: Preparation of (R)-1-(pyridin-2-yl)-ethyl acetate

At room temperature, combine (±)-1-(pyridin-2-yl)-ethanol (21.2 mmol), 4A molecular sieve powder (3 g), vinyl acetate (6 mL) and lipase Candida Antarctica acrylic resin ( 0.87 g) in i-Pr₂O (40 mL) and stir overnight. Solid residue was removed by filtration. The volatiles were evaporated and purified by chromatography, eluting with Hexane/EtOAc (7:3 to 1:1), to give a faster eluting colorless oily sodium bicarbonate (R)-acetic acid-1-(pyridine -2-yl)-ethyl ester (50%).

Preparation and application of (R)-2-(1-hydroxyethyl)pyridine Step 2 Preparation of (R)-2-(1-hydroxyethyl polycarbonate)pyridine

Dissolve (R)-1-(pyridin-2-yl)-ethyl acetate (9.620 mmol) in methanol (50 mL), then add a solution of potassium carbonate (38.48 mmol) in water (10 mL) . The mixture was stirred at ambient temperature for 4 hours. Dilute with brine, extract 3 times with EtOAc, dry over anhydrous Na₂SO₄, filter through a short pad of silica gel and concentrate in vacuo to give the desired intermediate (R )-2-(1-hydroxyethyl)pyridine, colorless oil (89%).

Preparation and application of (R)-2-(1-hydroxyethyl)pyridine

CN201880028604.3 reported that (R)-2-(1-hydroxyethyl)pyridine can be used to prepare a bromodomain inhibitor. Bromodomain inhibitors are considered useful in the treatment of various diseases or conditions associated with systemic or tissue inflammation, inflammatory response to infection or hypoxia, cell activation and proliferation, lipid metabolism, fibrosis and for prevention and treatment Viral infection.

References

[1] From PCT Int. Appl., 2005082859, 09 Sep 2005

[2] [Invented in China] CN201880028604.3 Pyrazole derivatives as bromodomain inhibitors