Acetonitrile → HCID 22144482, compound

Temperature

95 °C

A 185 mL Ace-Glass pressure tube was charged with 5-bromo-2-methoxypyridine (2.80 g, 14.9 mmol), N-methyl-N-(tert-butoxycarbonyl)-4-penten-2-amine (2.97 g, 14.9 mmol), prepared as previously described, palladium(II) acetate (33.4 mg, 0.149 mmol), tri-o-tolylphosphine (181 mg, 0.596 mmol), triethylamine (5 mL) and acetonitrile (10 mL). The tube was flushed with nitrogen, sealed, and the mixture was stirred and heated at 95° C. (oil bath temperature) for 18 h. The tube contents were cooled; more palladium(II) acetate (33.4 mg, 0.149 mmol) and tri-o-tolylphosphine (181 mg, 0.596 mmol) were added. The mixture was further stirred and heated at 94° C. for 20 h. TLC analysis (hexane-ethyl acetate (2:1)) indicated the presence of 5-bromo-2-methoxypyridine. Therefore, more palladium(II) acetate (33.4 mg, 0.149 mmol) and tri-o-tolylphosphine (181 mg, 0.596 mmol) were added, and the mixture was heated at 95° C. for an additional 20 h. The mixture was cooled and concentrated via rotary evaporator. The residue was diluted with water (35 mL) and extracted with dichloromethane (50 mL, 2×35 mL). The combined dichloromethane extracts were dried (Na2SO4), filtered, and concentrated under vacuum to produce a light-brown, oily semisolid (5.61 g). The crude product was purified by column chromatography on silica gel (70–230 mesh) (200 g) eluting with a hexane-ethyl acetate gradient (64:1→6:1). Fractions containing the product (Rf 0.28 in hexane-ethyl acetate (6:1)) were combined and concentrated under vacuum to give 2.36 g of an oily, yellow semisolid. Impure fractions were combined and concentrated to give 1.48 g of a light-yellow oil. This material was re-chromatographed on the silica gel (70–230 mesh) (95 g) eluting with the previously described hexane-ethyl acetate gradient (64:1→6:1). All fractions containing the product were combined and concentrated under vacuum to give 0.85 g of a light-yellow oil, bringing the total yield to 2.915 (63.9%).

1. customprepared
2. customThe tube was flushed with nitrogen
3. customsealed
4. temperatureThe tube contents were cooled
5. stirringThe mixture was further stirred
6. temperatureheated at 94° C. for 20 h
7. temperaturethe mixture was heated at 95° C. for an additional 20 h
8. temperatureThe mixture was cooled
9. concentrationconcentrated via rotary evaporator
10. additionThe residue was diluted with water (35 mL)
11. extractionextracted with dichloromethane (50 mL, 2×35 mL)
12. dry with materialThe combined dichloromethane extracts were dried (Na2SO4)
13. filtrationfiltered
14. concentrationconcentrated under vacuum

ORD record

ord-67f98f464ffa46efa2d7adc9f7ed3b4e

Source dataset

uspto-grants-2006_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07045538B2