Sodium hydride → HCID 58005107, compound

Participants

Reaction Steps

(4R)-1-(tert-butoxycarbonyl)-4-hydroxy-L-proline (1.0 eq.) in DMF was added to a 0° C. cooled suspension of 18-crown-6 (0.1 eq.) and NaH (3.0 eq.) in DMF (0.5 M final concentration). The reaction mixture was allowed to warm up to RT and stirred for 1 h. A 0.5M solution of 3-bromo-3′-(bromomethyl)biphenyl 95 (1.0 eq.) in DMF was added dropwise and the reaction mixture was stirred at RT overnight. The reaction mixture was quenched with aqueous HCl (1N) at 0° C. and diluted with EtOAc. The organic layer was separated, washed with aqueous HCl (1N) and brine, dried (Na2SO4) and evaporated to a solid. MS (ES+) m/z 498, 500 (M+Na)+. A 0.5 M solution of the crude material in a mixture of toluene:MeOH (2:1) was cooled to 0° C. and treated dropwise with TMS-diazomethane (1.5 eq.). The reaction mixture was allowed to warm up to RT and stirred for 1 h. The solvents were evaporated under reduced pressure and the residue was purified by flash chromatography (SiO2, PE:EtOAc=8:2) to afford the title compound 96 as a yellow oil (78%). 1H NMR (400 MHz, DMSO-d6, 300 K) δ 7.90-7.86 (m, 1H), 7.71 (d, J 7.7, 1H), 7.69-7.58 (m, 3H), 7.54-7.44 (m, 2H), 7.40 (d, J 7.7, 1H), 4.66-4.55 (m, 2H), 4.31-4.21 (m, 2H), 3.74-3.65 (m, 3H), 3.60-3.45 (m, 2H), 2.51-2.37 (m, 1H), 2.10-2.00 (m, 1H), 1.44-1.31 (m, 9H). MS (ES+) m/z 512, 514 (M+Na)+.

Provenance & Evidence