Sodium hydride → HCID 58577811, compound

Sodium hydride (60% disp. in oil, 908.0 mg, 22.72 mmol) was added portionwise at room temperature to a solution of 5-bromo-2-fluoropyridine A-5 (1.16 mL, 11.36 mmol) and methyl 3-hydroxy-2,2-dimethylpropanoate (1.88 mL, 14.77 mmol) in anhydrous tetrahydrofuran (32.9 mL) and anhydrous 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (5.0 mL) under an atmosphere of argon and in the presence of 4 Å molecular sieves. After 2 h of stirring at room temperature, the reaction mixture was heated at 50° C. for 10 h and then at 70° C. for 3 h. The suspension was cooled to room temperature, filtered over a thin celite pad, and the pad was rinsed with diethyl ether (150 mL). The filtrate was concentrated to a volume of ca. 5 mL, then diluted with diethyl ether (150 mL), quenched with water (90 mL) and decanted. The aqueous layer was extracted with diethyl ether (2×100 mL); the combined extracts were successively washed with water (3×70 mL), brine (70 mL), dried over anhydrous magnesium sulfate, filtered and concentrated to dryness under reduced pressure. The crude residue was purified by flash column chromatography on silica gel (100:0 to 80:20 hexanes:ethyl acetate gradient) to give methyl 3-(5-bromopyridin-2-yloxy)-2,2-dimethylpropanoate A-6 (1.796 g, Yield=55%). MS (ESI), [M+1]+ 288, 290.

1. temperaturethe reaction mixture was heated at 50° C. for 10 h
2. waitat 70° C. for 3 h
3. temperatureThe suspension was cooled to room temperature
4. filtrationfiltered over a thin celite pad
5. washthe pad was rinsed with diethyl ether (150 mL)
6. concentrationThe filtrate was concentrated to a volume of ca. 5 mL
7. additiondiluted with diethyl ether (150 mL)
8. customquenched with water (90 mL)
9. customdecanted
10. extractionThe aqueous layer was extracted with diethyl ether (2×100 mL)
11. washthe combined extracts were successively washed with water (3×70 mL), brine (70 mL)
12. dry with materialdried over anhydrous magnesium sulfate
13. filtrationfiltered
14. concentrationconcentrated to dryness under reduced pressure
15. customThe crude residue was purified by flash column chromatography on silica gel (100:0 to 80:20 hexanes:ethyl acetate gradient)

ORD record

ord-7936a6c6df204d05b555b574d7d1766b

Source dataset

uspto-grants-2014_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08637507B2