Walker, Shawn D.; Borths, Christopher J.; DiVirgilio, Evan; Huang, Liang; Liu, Pingli; Morrison, Henry; Sugi, Kiyoshi; Tanaka, Masahide; Woo, Jacqueline C. S.; Faul, Margaret M. published an article in Organic Process Research & Development. The title of the article was 《Development of a Scalable Synthesis of a GPR40 Receptor Agonist》.Recommanded Product: (S)-3-(4-Hydroxyphenyl)hex-4-ynoic acid The author mentioned the following in the article:
Early process development and salt selection for AMG 837, a novel GPR40 receptor agonist, is described. The synthetic route to AMG 837 involved the convergent synthesis and coupling of two key fragments, (S)-3-(4-hydroxyphenyl)hex-4-ynoic acid (I) and 3-(bromomethyl)-4′-(trifluoromethyl)biphenyl (II). The chiral β-alkynyl acid I was prepared in 35% overall yield via classical resolution of the corresponding racemic acid (±)-I. An efficient and scalable synthesis of (±)-I was achieved via a telescoped sequence of reactions including the conjugate alkynylation of an in situ protected Meldrum’s acid derived acceptor. The biaryl bromide II was prepared in 86% yield via a 2-step Suzuki-Miyaura coupling-bromination sequence. Chemoselective phenol alkylation mediated by tetrabutylphosphonium hydroxide allowed direct coupling of I and II to afford AMG 837. Due to the poor physiochem. stability of the free acid form of the drug substance, a sodium salt form was selected for early development, and a more stable, crystalline hemicalcium salt dihydrate form was subsequently developed. Overall, the original 12-step synthesis of AMG 837 was replaced by a robust 9-step route affording the target in 25% yield. The experimental part of the paper was very detailed, including the reaction process of (S)-3-(4-Hydroxyphenyl)hex-4-ynoic acid(cas: 865233-35-8Recommanded Product: (S)-3-(4-Hydroxyphenyl)hex-4-ynoic acid)
(S)-3-(4-Hydroxyphenyl)hex-4-ynoic acid(cas: 865233-35-8) belongs to alkynes. The addition of nonpolar E−H bonds across C≡C is general for silanes, boranes, and related hydrides.Recommanded Product: (S)-3-(4-Hydroxyphenyl)hex-4-ynoic acid The hydroboration of alkynes gives vinylic boranes which oxidize to the corresponding aldehyde or ketone. In the thiol-yne reaction the substrate is a thiol.
Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts