Hydrochloric Acid → 3-(methoxymethyl)-5-methylisoxazol-4-ylboronic acid

Temperature

-78 °C

n-Butyl lithium (2.5 M in hexanes, 2.20 mmol) was added dropwise to 4-bromo-3-methoxymethyl-5-methyl isoxazole (412 mg, 2.00 mmol) in THF (8 mL) at −78° C. under nitrogen. After stirring at −78° C. for 30 min triisopropylborate (564 mg, 3.00 mmol) was added dropwise. The temperature was maintained at −78° C. for 2 h then the reaction was allowed to warm to room temperature and stirred for 15 h. The reaction mixture was poured into a mixture of 1N hydrochloric acid and water (1:1, 100 mL) and stirred rapidly for 1 h. The organic layer was separated and the aqueous layer was extracted with ether (3×25 mL). The combined organic layers were washed with brine (25 mL), dried over magnesium sulfate, filtered and evaporated to dryness. The residue was triturated with hexanes (30 mL) then dried under high vacuum to provide 89 mg (29% yield) of 3-methoxymethyl-5-methyl isoxazole-4-boronic acid as a waxy tan solid which was immediately carried forward to the next reaction: 1H NMR (300 MHz, CDCl3) δ ppm 4.74 (s, 2H), 3.37 (s, 3H), 2.74 (s, 3H), 2.60 (s, 2H).

1. additionwas added dropwise
2. temperatureto warm to room temperature
3. stirringstirred rapidly for 1 h
4. customThe organic layer was separated
5. extractionthe aqueous layer was extracted with ether (3×25 mL)
6. washThe combined organic layers were washed with brine (25 mL)
7. dry with materialdried over magnesium sulfate
8. filtrationfiltered
9. customevaporated to dryness
10. customThe residue was triturated with hexanes (30 mL)
11. customthen dried under high vacuum

ORD record

ord-a403a52b5d354122b58fb1975a774f0b

Source dataset

uspto-grants-2011_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07884107B2