(Z)-methyl 2-bromo-9-(trifluoromethylsulfonyloxy)-6,7-dihydro-5H-benzo[7]annulene-8-carboxylate → (E)-methyl 2-bromo-9-methyl-6,7-dihydro-5H-benzo[7]annulene-8-carboxylate

To a suspension of CuI (760 mg, 4.0 mmol) in anhydrous diethyl ether (5 mL) was dropwise added a 1.6 M solution of methyllithium (8 mmol, 5 mL) in an ice-salt bath (−10° C.). After stirring for 20 min, a homogeneous 0.4 M (Me)2CuLi solution was ready for use. To a solution of (Z)-methyl 2-bromo-9-(trifluoromethylsulfonyloxy)-6,7-dihydro-5H-benzo[7]annulene-8-carboxylate from step B1 (52 mg, 0.121 mmol) in diethyl ether (0.5 mL) was dropwise added the above Me2CuLi solution (0.727 mmol, 1.82 mL) at −78° C. The mixture was stirred from −78° C. to −40° C. over 2 h. The reaction mixture was then quenched with 10 mL of water, and the mixture was extracted with diethyl ether (3×15 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo to give (E)-methyl 2-bromo-9-methyl-6,7-dihydro-5H-benzo[7]annulene-8-carboxylate (38 mg, 0.129 mmol, 106% yield). The material was used for the next step without purification. LCMS (M+H)+=297.0. 1H NMR (500 MHz, chloroform-d) δ 7.43 (d, J=1.8 Hz, 1H), 7.35 (dd, J=8.1, 2.0 Hz, 1H), 7.07 (d, J=8.2 Hz, 1H), 3.82 (s, 3H), 2.56-2.49 (m, 2H), 2.38 (s, 3H), 2.17-2.07 (m, 4H).

1. stirringThe mixture was stirred from −78° C. to −40° C. over 2 h
2. customThe reaction mixture was then quenched with 10 mL of water
3. extractionthe mixture was extracted with diethyl ether (3×15 mL)
4. dry with materialThe combined organic layers were dried over sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated in vacuo

ORD record

ord-db2a8b68bf99405a9190ce98546f0962

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08604024B2