n-Hexyl bromide; 1-Bromohexane -Drug Synthesis Database

【结构式】

【分子编号】11108

【品名】n-Hexyl bromide; 1-Bromohexane

【CA登记号】111-25-1

【分子式】C₆H₁₃Br

【分子量】165.07322

【元素组成】C 43.66% H 7.94% Br 48.41%

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：

The demethylation ot o-vanillin (I) with AlCl3 dissolved in pyridine gives 2,3 dihydroxybenzaldehyde (II). Subsequent alkylation by means of hexyl bromide with NaH gives 3-hexyloxy-2-hydroxybenzaldehyde (III), which is then condensed with malononitrile and piperidine, yielding 3-cyano-8-hexyloxycromen-2-one (IV), a needle-like yellow crystalline substance. Finally, compound (IV) is treated with sodium azide and AlCl3 in refluxing THF, yielding the formation of the tetrazole ring.

参考文献中间体

合成目标

【1】 Tasaka, K.; KP-136. Drugs Fut 1988, 13, 10, 915.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	10158	Piperidine	110-89-4	C₅H₁₁N	详情	详情
	11108	n-Hexyl bromide; 1-Bromohexane	111-25-1	C₆H₁₃Br	详情	详情
(I)	12620	o-Vanillin; 2-Hydroxy-3-methoxybenzaldehyde	148-53-8	C₈H₈O₃	详情	详情
(II)	12380	2,3-Dihydroxybenzaldehyde	24677-78-9	C₇H₆O₃	详情	详情
(III)	23096	3-(hexyloxy)-2-hydroxybenzaldehyde		C₁₃H₁₈O₃	详情	详情
(IV)	23097	8-(hexyloxy)-2-oxo-2H-chromene-3-carbonitrile		C₁₆H₁₇NO₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(LI)

Oxetanone (XLV) can also be obtained as follows: The reaction of 3(R)-hydroxytetradecanoic acid tert-butyl ester (XLVI) with DHP and p-toluenesulfonic acid gives the corresponding tetrahydropyranyl ether (XLVII), which is reduced with dibutylaluminum hydride (DIBAL) in toluene to the aldehyde (XI), already obtained. Compound (XI) is condensed with 2-(p-toluenesulfinyl)acetic acid tert-butyl ester (XLVIII) by means of tert-butylmagnesium bromide in ether-THF affording the sulfinylhydroxy ester (II), which is treated with aluminum amalgam in THF-water to yield the hydroxy ester (L). The alkylation of (L) with hexyl bromide (LI) by means of butyllithium and diisopropylamine in THF-hexane affords 2-hexyl-3(S)-hydroxy-5(R)-(tetrahydropyranyloxy)hexadecanoic acid tert-butyl ester (LII), which is hydrolyzed with KOH in methanol to the corresponding free acid (LIII). The lactonization of (LIII) with pyridinium p-toluenesulfonate in hot ethanol affords oxetanone (LIV) as a diastereomeric mixture, which is separated by column chromatography, finally yielding oxetanone (XLV), previously obtained in scheme 11082301c.

参考文献中间体

合成目标

【1】 Barbier, P.; Schneider, F.; Synthesis of tetrahydrolipstatin and tetrahydroesterastin, compounds with beta-lactone moiety. Stereoselective hydrogenation of a beta-keto delta-lactone and conversion of the delta-lactone into a beta-lactone. J Org Chem 1988, 53, 6, 1218-21.
【2】 Prous, J.; Mealy, N.; Castaner, J.; Orlistat. Drugs Fut 1994, 19, 11, 1003.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IL)	11106	tert-butyl (3S,5R)-3-hydroxy-2-[(4-methylphenyl)sulfinyl]-5-(tetrahydro-2H-pyran-2-yloxy)hexadecanoate		C₃₂H₅₄O₆S	详情	详情
(XLV)	11102	(3S,4S)-3-Hexyl-4-[(2R)-2-(tetrahydro-2H-pyran-2-yloxy)tridecyl]-2-oxetanone		C₂₇H₅₀O₄	详情	详情
(XLVI)	11103	tert-butyl (3R)-3-hydroxytetradecanoate		C₁₈H₃₆O₃	详情	详情
(XLVII)	11104	tert-butyl (3R)-3-(tetrahydro-2H-pyran-2-yloxy)tetradecanoate		C₂₃H₄₄O₄	详情	详情
(XLVIII)	11105	tert-butyl 2-[(4-methylphenyl)sulfinyl]acetate		C₁₃H₁₈O₃S	详情	详情
(L)	11107	tert-butyl (3S,5R)-3-hydroxy-5-(tetrahydro-2H-pyran-2-yloxy)hexadecanoate		C₂₅H₄₈O₅	详情	详情
(LI)	11108	n-Hexyl bromide; 1-Bromohexane	111-25-1	C₆H₁₃Br	详情	详情
(LII)	11109	tert-butyl (3S,5R)-2-hexyl-3-hydroxy-5-(tetrahydro-2H-pyran-2-yloxy)hexadecanoate		C₃₁H₆₀O₅	详情	详情
(LIII)	11110	(3S,5R)-2-Hexyl-3-hydroxy-5-(tetrahydro-2H-pyran-2-yloxy)hexadecanoic acid		C₂₇H₅₂O₅	详情	详情
(LIV)	63075	(4S)-3-hexyl-4-[(2R)-2-(tetrahydro-2H-pyran-2-yloxy)tridecyl]-2-oxetanone		C₂₇H₅₀O₄	详情	详情

Extended Information