4-methyl-1-octyn-4-ol -Drug Synthesis Database

【结构式】

【分子编号】29066

【品名】4-methyl-1-octyn-4-ol

【CA登记号】

【分子式】C₉H₁₆O

【分子量】140.22544

【元素组成】C 77.09% H 11.5% O 11.41%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(III)

The Grignard reaction of propargylmagnesium bromide (I) with 2-hexanone (II) in ether gives 4-methyloct-1-in-4-ol (III), which by reaction with diisobutylaluminum hydride and I2 is converted to 1-iodo-4-methyloct-1-en-4-ol (IV). The reaction of (IV) with dihydropyran and p-toluenesulfonic acid yields the corresponding tetrahydropyranyloxy derivative (V), which by reaction with tert-butyllithium and copper pentyne (VI) affords the corresponding organolithiocuprate (VII). The condensation of (VII) with 4R-(tetrahydropyranyloxy)-2-[7-(tetrahydropyranyloxyl)heptyl]cyclopent-2-en-1-one (VIII) in ether gives 1,11,16-tris(tetrahydropyranyloxy)-16-methylprost-13-en-9-one (IX), which is finally deprotected by a treatment with acetic acid in water THF.

参考文献中间体

合成目标

【1】 Woessner, W.D.; Biddlecom, W.G.; Kluender, H.C. (Bayer Corp.); Preparation of 15-deoxy-16-hydroxyprostaglandins. US 4132738 .
【2】 Castaner, J.; Serradell, M.N.; Rioprostil. Drugs Fut 1985, 10, 3, 207.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	29064	bromo(2-propynyl)magnesium		C₃H₃BrMg	详情	详情
(II)	29065	2-hexanone	591-78-6	C₆H₁₂O	详情	详情
(III)	29066	4-methyl-1-octyn-4-ol		C₉H₁₆O	详情	详情
(IV)	29067	(E)-1-iodo-4-methyl-1-octen-4-ol		C₉H₁₇IO	详情	详情
(V)	29068	(E)-2-butyl-5-iodo-2-methyl-4-pentenyl tetrahydro-2H-pyran-2-yl ether		C₁₅H₂₇IO₂	详情	详情
(VI)	29069	1-pentynylcopper		C₅H₇Cu	详情	详情
(VIII)	29070	(4R)-4-[(tetrahydro-2H-pyran-2-yloxy)methyl]-2-[8-(tetrahydro-2H-pyran-2-yloxy)octyl]-2-cyclopenten-1-one		C₂₄H₄₀O₅	详情	详情
(IX)	29071	(2R,3S,4R)-3-[(E)-4-methyl-4-[(tetrahydro-2H-pyran-2-yloxy)methyl]-1-octenyl]-4-[(tetrahydro-2H-pyran-2-yloxy)methyl]-2-[8-(tetrahydro-2H-pyran-2-yloxy)octyl]cyclopentanone		C₃₉H₆₈O₇	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

The sililation of 4-methyl-1-octin-4-ol (I) with trimethylsilyl chloride by means of triethylamine in DMF gives the corresponding silyloxy derivative (II), which is treated with diisobutyl aluminum hydride and I2 in toluene - THF yielding 4-methyl-(RS)-4-trimethylsilyloxy-trans-1-octene-1-yl iodide (III). The condensation of (III) with the complex of copper 1-pentynilyde and HMPT (IV) by means of butyllithium in hexane affords the complex salt (V), which, without isolation, is allowed to react with methyl 7-[3-[(RS)-tetrahydropyranyl-2-oxy]-5-oxo-1-cyclopentenyl]-heptanoate (VI) in ethyl ether to give methyl 7-[3-(tetrahydropyranyl-2-oxy)-2-(4-methyl-4-trimethylsilyloxy-trans-1-octene-1-yl)-5-oxo-cyclopentyl]heptanoate (VII). Finally, this compound is hydrolyzed with a mixture acetic acid - water - THF at room temperature.

参考文献中间体

合成目标

【1】 Collins P.W.; et al.; Influence of the position of the side-chain hydroxy group on the biological properties of prostaglandins. Tetrahedron Lett 1975, 48, 4217-20.
【2】 Pappo, R.; Collins, P.W.; 16-Oxygenated prostanoic acid derivatives. BE 0827127; DE 2513212; FR 2274289; GB 1492426; JP 50135059; US 3965143 .
【3】 Castaner, J.; Hillier, K.; SC-29333. Drugs Fut 1977, 2, 12, 817.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	29066	4-methyl-1-octyn-4-ol	C₉H₁₆O	详情	详情
(II)	33906	1-butyl-1-methyl-3-butynyl trimethylsilyl ether; [(1-butyl-1-methyl-3-butynyl)oxy](trimethyl)silane	C₁₂H₂₄OSi	详情	详情
(III)	33907	[[(E)-1-butyl-4-iodo-1-methyl-3-butenyl]oxy](trimethyl)silane; (E)-1-butyl-4-iodo-1-methyl-3-butenyl trimethylsilyl ether	C₁₂H₂₅IOSi	详情	详情
(IV)	29069	1-pentynylcopper	C₅H₇Cu	详情	详情
(V)	33908		C₁₇H₃₂CuLiOSi	详情	详情
(VI)	33909	methyl 7-[(1R,4S)-2-oxo-4-[(tetrahydro-2H-pyran-2-yloxy)methyl]cyclopentyl]heptanoate	C₁₉H₃₂O₅	详情	详情
(VII)	33910	methyl 7-[(1R,2S,3R)-2-[(E)-4-methyl-4-[(trimethylsilyl)oxy]-1-octenyl]-5-oxo-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]cyclopentyl]heptanoate	C₃₁H₅₆O₆Si	详情	详情

Extended Information