Hydrochloric Acid → (5-(Benzyloxy)-2-methoxyphenyl)(5-methylthiazol-2-yl)methanone

Temperature

-78 °C

To a stirring mixture of 5-methylthiazole (3.80 g, 38.2 mmol) in dry THF (200 mL) was added n-BuLi (2.5 M in hexane, 15.3 mL, 38.2 mmol) drop wise over 20 minutes at −78° C. under nitrogen atmosphere. The mixture was stirred between −78° C. and −60° C. for 1.5 h and then cooled to −78° C. A solution of methyl 5-(benzyloxy)-2-methoxybenzoate (10.4 g, 38.2 mmol) in THF (50 mL) was added drop wise over 30 minutes. The resulting mixture was stirred at −78° C. for 30 minutes and warmed to room temperature with stirring overnight. The mixture was cooled to 0° C. and treated with water (50 mL). The resulting mixture was adjusted to pH around 6 with HCl (1N). The organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluting with petroleum ether/EtOAc (3:1) to afford (5-(benzyloxy)-2-methoxyphenyl)(5-methylthiazol-2-yl)methanone (2.5 g, 19%) as a yellow gel. 3.0 g of starting material methyl 5-(benzyloxy)-2-methoxybenzoate was recovered.

1. stirringThe resulting mixture was stirred at −78° C. for 30 minutes
2. temperaturewarmed to room temperature
3. stirringwith stirring overnight
4. temperatureThe mixture was cooled to 0° C.
5. dry with materialThe organic layer was dried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. customThe residue was purified by silica gel column chromatography
9. washeluting with petroleum ether/EtOAc (3:1)

ORD record

ord-9addde1389b4455f83a8b34bdab3bdca

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09199947B2