Methanol → 2-[2-(5-Bromo-2-methoxy-phenyl)-ethyl]-thiophene-3-carboxylic acid

To a solution of 2-methyl-thiophene-3-carboxylic acid (8.01 g, 56.0 mmol, 1.0 equiv) in THF (56 mL) at −78° C. was added a solution of lithium diisopropylamide (LDA; 2M, 56 mL, 112.0 mmol, 2 equiv). The orange solution was allowed to stir for 1 hr and then a solution of 4-bromo-2-bromomethyl-1-methoxybenzene (17 g, 73 mmol, 1.3 equiv) in THF (50 mL) was added dropwise via cannula. The solution was allowed to stir at −78° C. for one hour and then warmed to room temperature. The reaction was quenched by the addition of water and ethyl acetate. The phases were separated and the organic phase was washed with brine, dried over Na2SO4, filtered, and concentrated to give a yellow oil. Addition of methanol caused precipitation of a white solid, which was filtered and dried to give 2-[2-(5-bromo-2-methoxy-phenyl)-ethyl]-thiophene-3-carboxylic acid (5.3 g, 15.5 mmol, 27%). 1H NMR (300 MHz, d6-DMSO) δ 12.59 (s, 1H), 7.31 (dd, J=8.7, 5.7 Hz, 1H), 7.26 (dd, J=6.6, 5.4 Hz, 2H), 7.21 (d, J=2.4 Hz, 1H), 6.88 (d, J=9.0 Hz, 1H), 3.71 (s, 3H), 3.27-3.35 (m, 2H), and 2.79-2.88 (m, 2H). LCMS ES− 339 (M−1), 341 (M+1).

1. stirringto stir at −78° C. for one hour
2. customThe reaction was quenched by the addition of water and ethyl acetate
3. customThe phases were separated
4. washthe organic phase was washed with brine
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated
8. customto give a yellow oil
9. customprecipitation of a white solid, which
10. filtrationwas filtered
11. customdried

ORD 기록

ord-016a62db01b2415c83ddf012fdfb98f4

출처 데이터셋

uspto-grants-2010_09

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US07790719B2