triethyl phosphite -Drug Synthesis Database

【结构式】

【分子编号】15487

【品名】triethyl phosphite

【CA登记号】122-52-1

【分子式】C₆H₁₅O₃P

【分子量】166.157062

【元素组成】C 43.37% H 9.1% O 28.89% P 18.64%

与该中间体有关的原料药合成路线共 4 条

合成路线1 合成路线2 合成路线3 合成路线4

合成路线1

该中间体在本合成路线中的序号：(I)

The reduction of triethyl phosphite (I) with ethyl chloroformate (II) gives phosphonoformic acid triethyl ester (III), which is hydrolyzed with refluxing aqueous NaOH. Other alkyl esters can be used instead.

参考文献中间体

合成目标

【1】 McIntosh, C.L.; Carboxyphosphonates. US 4018854 .
【2】 McIntosh, C.L.; Carboxyphosphonate brush control agents. US 4042650 .
【3】 Castaner, J.; Blancafort, P.; Hopkins, S.J.; Serradell, M.N.; Foscarnet sodium. Drugs Fut 1980, 5, 7, 345.

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)	15487	triethyl phosphite	122-52-1	C₆H₁₅O₃P	详情	详情
(II)	11229	1-[(Chlorocarbonyl)oxy]ethane;ethyl carbonochloridate; Carbonchloridic acid ethyl ester;Ethyl chloroformate;Ethyl chlorocarbonate	541-41-3	C₃H₅ClO₂	详情	详情
(III)	32722	Ethyl diethoxy(oxo)phosphoranecarboxylate; Phosphonoformic acid triethyl ester	1474-78-8	C₇H₁₅O₅P	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IX)

The intermediate phosphonate (X) has been obtained as follows. The cyclization of thioacetamide (IV) with ethyl 3-bromopiruvate (V) in ethanol gives 2-methylthiazole-4-carboxylic acid ethyl ester (VI), which is reduced by means of LiAlH4 in ethyl ether to yield the carbinol (VII). The bromination of (VII) with CBr4 and PPh3 in CCl4 affords the 4-bromomethyl-2-methylthiazole (VIII), which is finally condensed with triethyl phosphite (IX) to provide the target phosphonate intermediate (X). Alternatively, the cyclization of thioacetamide (IV) with 1,3-dichloroacetone (XI) gives 4-(chloromethyl)-2-methylthiazole (XII), which is condensed with triethyl phosphite (IX) to also provide the target phosphonate intermediate (X).

参考文献中间体

合成目标

【1】 Jung, J.-K.; Kache, R.; Vines, K.K.; Zheng, Y.-S.; Avery, M.A.; Total synthesis of epothilones B and D amenable to large-scale preparation. 225th ACS Natl Meet (March 23 2003, New Orleans) 2003, Abst MEDI 121.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IV)	19170	ethanethioamide	62-55-5	C₂H₅NS	详情	详情
(V)	63904	propyl 3-bromo-2-oxopropanoate		C₆H₉BrO₃	详情	详情
(VI)	63905	propyl 2-methyl-1,3-thiazole-4-carboxylate		C₈H₁₁NO₂S	详情	详情
(VII)	63906	(2-methyl-1,3-thiazol-4-yl)methanol		C₅H₇NOS	详情	详情
(VIII)	63909	4-(bromomethyl)-2-methyl-1,3-thiazole		C₅H₆BrNS	详情	详情
(IX)	15487	triethyl phosphite	122-52-1	C₆H₁₅O₃P	详情	详情
(X)	63908	dipropyl (2-methyl-1,3-thiazol-4-yl)methylphosphonate		C₁₁H₂₀NO₃PS	详情	详情
(XI)	63907	1,3-dichloroacetone		C₃H₄Cl₂O	详情	详情
(XII)	40819	4-(chloromethyl)-2-methyl-1,3-thiazole		C₅H₆ClNS	详情	详情

合成路线3

该中间体在本合成路线中的序号：(IX)

参考文献中间体

合成目标

【1】 Jung, J.-K.; Kache, R.; Vines, K.K.; Zheng, Y.-S.; Avery, M.A.; Total synthesis of epothilones B and D amenable to large-scale preparation. 225th ACS Natl Meet (March 23 2003, New Orleans) 2003, Abst MEDI 121.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IV)	19170	ethanethioamide	62-55-5	C₂H₅NS	详情	详情
(V)	63904	propyl 3-bromo-2-oxopropanoate		C₆H₉BrO₃	详情	详情
(VI)	63905	propyl 2-methyl-1,3-thiazole-4-carboxylate		C₈H₁₁NO₂S	详情	详情
(VII)	63906	(2-methyl-1,3-thiazol-4-yl)methanol		C₅H₇NOS	详情	详情
(VIII)	63909	4-(bromomethyl)-2-methyl-1,3-thiazole		C₅H₆BrNS	详情	详情
(IX)	15487	triethyl phosphite	122-52-1	C₆H₁₅O₃P	详情	详情
(X)	63908	dipropyl (2-methyl-1,3-thiazol-4-yl)methylphosphonate		C₁₁H₂₀NO₃PS	详情	详情
(XI)	63907	1,3-dichloroacetone		C₃H₄Cl₂O	详情	详情
(XII)	40819	4-(chloromethyl)-2-methyl-1,3-thiazole		C₅H₆ClNS	详情	详情

合成路线4

该中间体在本合成路线中的序号：(II)

The reaction of 1,3-dibromopropane (I) with triethyl phosphite (II) at 160 C gives triethyl 3-bromopropylphosphonate (III), which is treated with Tms-Br and water to yield the corresponding phosphonic acid (IV). The reaction of (IV) with PCl3 in refluxing chloroform affords the acyl chloride (V), which is treated with 4-methoxyphenol (VI) and pyridine to provide the expected 4-methoxyphenyl diester (VII). The reaction of (VII) with N,O-bis(tert-butoxycarbonyl)hydroxylamine (VIII) by means of NaH in DMF gives the fully protected hydroxyamino derivative (IX), which by treatment with TFA in dichloromethane yields 3-(hydroxyamino)propylphosphonic acid 4-methoxyphenyl diester (X). Finally, this compound is acylated with Ac-Cl and TEA in ethyl ether to afford the target N-acetylhydroxyamino compound.

参考文献中间体

合成目标

【1】 Reichenberg, A.; et al.; Diaryl ester prodrugs of FR900098 with improved in vivo antimalarial activity. Bioorg Med Chem Lett 2001, 11, 6, 833.

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)	12581	1,3-Dibromopropane	109-64-8	C₃H₆Br₂	详情	详情
(II)	15487	triethyl phosphite	122-52-1	C₆H₁₅O₃P	详情	详情
(III)	39080	diethyl 3-bromopropylphosphonate		C₇H₁₆BrO₃P	详情	详情
(IV)	39105	3-bromopropylphosphonic acid	1190-09-6	C₃H₈BrO₃P	详情	详情
(V)	49412	3-bromopropylphosphonic dichloride		C₃H₆BrCl₂OP	详情	详情
(VI)	32744	4-methoxyphenol	150-76-5	C₇H₈O₂	详情	详情
(VII)	49413	bis(4-methoxyphenyl) 3-bromopropylphosphonate		C₁₇H₂₀BrO₅P	详情	详情
(VIII)	34722	2-[([[(tert-butoxycarbonyl)amino]oxy]carbonyl)oxy]-2-methylpropane		C₁₀H₁₉NO₅	详情	详情
(IX)	49414	5-(tert-butoxycarbonyl)-1,1-bis(4-methoxyphenoxy)-9,9-dimethyl-1,7-dioxo-6,8-dioxa-5-aza-1lambda(5)-phosphadecane		C₂₇H₃₈NO₁₀P	详情	详情
(X)	49415	bis(4-methoxyphenyl) 3-(hydroxyamino)propylphosphonate		C₁₇H₂₂NO₆P	详情	详情

Extended Information