1-Chloro-4-iodobutane → 6-Chloro-2-(4-(2,2-difluoroethoxy)phenyl)hexanoic acid

Participants

Reaction Steps

Step AX (2): 2-(4-(2,2-Difluoroethoxy)phenyl)acetic acid (6.00 g, 27.8 mmol) was deprotonated with NaHMDS (2.0 M in THF, 41.6 mL, 83 mmol) and reacted with 1-chloro-4-iodobutane (9.10 g, 41.6 mmol) using a procedure analogous to Step AC (1) to afford 6-chloro-2-(4-(2,2-difluoroethoxy)phenyl)hexanoic acid (6.94 g, 21.5 mmol, 77% yield) as a viscous oil that slowly solidified at rt to afford an off-white solid. LC-MS (M−H)− 305.21. 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 7.24 (d, J=8.9 Hz, 2 H), 6.87 (d, J=8.5 Hz, 2 H), 5.88-6.23 (m, 1 H), 4.15 (td, J=13.0, 4.1 Hz, 2 H), 3.44-3.53 (m, 3 H), 1.99-2.12 (m, 1 H), 1.70-1.86 (m, 3 H), 1.31-1.50 (m, 2 H).

Provenance & Evidence