tert-butyl (6R,7S,8S)-11-(9-borabicyclo[3.3.1]non-9-yl)-4,4,6,8-tetramethyl-3,5-dioxo-7-[[(2,2,2-trichloroethoxy)carbonyl]oxy]undecanoate -Drug Synthesis Database

【结构式】

【分子编号】26245

【品名】tert-butyl (6R,7S,8S)-11-(9-borabicyclo[3.3.1]non-9-yl)-4,4,6,8-tetramethyl-3,5-dioxo-7-[[(2,2,2-trichloroethoxy)carbonyl]oxy]undecanoate

【CA登记号】

【分子式】C₃₀H₄₈BCl₃O₇

【分子量】637.87602

【元素组成】C 56.49% H 7.58% B 1.69% Cl 16.67% O 17.56%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号：(VII)

Treatment of diketoester (I) with trimethylsilyl diazomethane and diisopropyl ethylamine produced enol ether (II). This was condensed with (S)-2-methyl-4-pentenal (III) in the presence of LDA at -120 C to afford the aldol condensation product (IV) as the major isomer. Protection of the 7-hydroxyl group of (IV) with trichloroethoxycarbonyl chloride gave carbonate (V). Enol ether of (V) was then hydrolyzed with p-TsOH in acetone to provide diketoester (VI). Hydroboration of the terminal olefin of (VI) with 9-borabicyclo[3.3.1]nonane gave organoborane (VII). Then, Suzuki coupling of (VII) with vinyl iodide (VIII), followed by acid hydrolysis of the silyl protecting group, provided the thiazolyl heptadecadienoate (IX). Asymmetric hydrogenation of 3-keto group of (IX) in the presence of the modified Noyori's catalyst [RuCl2(R)-BINAP)]2[Et3N] furnished the desired 3-(S) alcohol (X).

参考文献中间体

合成目标

【1】 Harris, C.R.; et al.; New chemical synthesis of the promising cancer chemotherapeutic agent 12,13-desoxyepothilone B: Discovery of a surprising long-range effect on the diastereoselectivity of an aldol condensation. J Am Chem Soc 1999, 121, 30, 7050.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	13664	1,1,1-Trichloro-2-[(chlorocarbonyl)oxy]ethane; 2,2,2-Trichloroethyl chloroformate	17341-93-4	C₃H₂Cl₄O₂	详情	详情
(I)	26239	tert-butyl 4,4-dimethyl-3,5-dioxoheptanoate		C₁₃H₂₂O₄	详情	详情
(II)	26240	tert-butyl (Z)-3-methoxy-4,4-dimethyl-5-oxo-2-heptenoate		C₁₄H₂₄O₄	详情	详情
(III)	26241	(2S)-2-methyl-4-pentenal		C₆H₁₀O	详情	详情
(IV)	26242	tert-butyl (2Z,6R,7S,8S)-7-hydroxy-3-methoxy-4,4,6,8-tetramethyl-5-oxo-2,10-undecadienoate		C₂₀H₃₄O₅	详情	详情
(V)	26243	tert-butyl (2Z,6R,7S,8S)-3-methoxy-4,4,6,8-tetramethyl-5-oxo-7-[[(2,2,2-trichloroethoxy)carbonyl]oxy]-2,10-undecadienoate		C₂₃H₃₅Cl₃O₇	详情	详情
(VI)	26244	tert-butyl (6R,7S,8S)-4,4,6,8-tetramethyl-3,5-dioxo-7-[[(2,2,2-trichloroethoxy)carbonyl]oxy]-10-undecenoate		C₂₂H₃₃Cl₃O₇	详情	详情
(VII)	26245	tert-butyl (6R,7S,8S)-11-(9-borabicyclo[3.3.1]non-9-yl)-4,4,6,8-tetramethyl-3,5-dioxo-7-[[(2,2,2-trichloroethoxy)carbonyl]oxy]undecanoate		C₃₀H₄₈BCl₃O₇	详情	详情
(VIII)	26246	tert-butyl(dimethyl)silyl (1S,3Z)-4-iodo-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3-pentenyl ether; 4-((1E,3S,5Z)-3-[[tert-butyl(dimethyl)silyl]oxy]-6-iodo-2-methyl-1,5-heptadienyl)-2-methyl-1,3-thiazole		C₁₈H₃₀INOSSi	详情	详情
(IX)	26247	tert-butyl (6R,7S,8S,12Z,15S,16E)-15-hydroxy-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-3,5-dioxo-7-[[(2,2,2-trichloroethoxy)carbonyl]oxy]-12,16-heptadecadienoate		C₃₄H₅₀Cl₃NO₈S	详情	详情
(X)	26248	tert-butyl (3S,6R,7S,8S,12Z,15S,16E)-3,15-dihydroxy-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-7-[[(2,2,2-trichloroethoxy)carbonyl]oxy]-12,16-heptadecadienoate		C₃₄H₅₂Cl₃NO₈S	详情	详情

Extended Information