Hydrochloric Acid → 5-Isobutyl-3,3-dimethyl-2,3-dihydrobenzofuran-7-boronic acid

Temperature

-78 °C

To a mixture of 7-bromo-5-isobutyl-3,3-dimethyl-2,3-dihydro-benzofuran (9.9 g, 34.96 mmol) in THF (50 mL) cooled to −78° C. under an atmosphere of argon was added n-BuLi (25.17 mL, 2.5 M, 62.93 mmol) dropwise. The reaction mixture was stirred for 5 minutes and triisopropylborate (24.2 mL, 104.87 mmol) was added dropwise. The mixture was stirred at −50° C. for 2 hours then warmed up to room temperature and stirred overnight at room temperature. 1.0 N HCl (100 mL) was slowly added to the reaction mixture. After 1 hour the mixture was diluted with ethyl acetate and the layers separated. The organic layer was further washed with water, brine, dried (Mg2SO4), filtered and evaporated. The residue was chromatographed on silica gel (0 to 20% ethyl acetate in hexane) to give 4.3 g of 5-isobutyl-3,3-dimethyl-2,3-dihydro-benzofuran-7-boronic acid (46%). 1H NMR (300 MHz; CDCL3): 0.90 (d, J=6.6 Hz, 6 H), 1.33 (s, 6 H), 1.81 (m, 1 H), 2.43 (d, J=7.5 Hz, 2 H), 4.28 (s, 2 H), 5.86 (br s, 2 H), 6.98 (d, J=2.1 Hz, 1 H), 7.33 (d, J=2.1 Hz, 1 H).

1. stirringThe mixture was stirred at −50° C. for 2 hours
2. temperaturethen warmed up to room temperature
3. stirringstirred overnight at room temperature
4. customthe layers separated
5. washThe organic layer was further washed with water, brine
6. dry with materialdried (Mg2SO4)
7. filtrationfiltered
8. customevaporated
9. customThe residue was chromatographed on silica gel (0 to 20% ethyl acetate in hexane)

ORD record

ord-b5bf0860457b4e248df486a68c484723

Source dataset

uspto-grants-2006_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07071218B2