ethyl 2-(hydroxymethyl)acrylate -Drug Synthesis Database

【结构式】

【分子编号】11327

【品名】ethyl 2-(hydroxymethyl)acrylate

【CA登记号】10029-04-6

【分子式】C₆H₁₀O₃

【分子量】130.1436

【元素组成】C 55.37% H 7.74% O 36.88%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(I)

An improved synthesis of ilmofosine has been reported: The reaction of 2-(hydroxymethyl)-2-propenoic acid ethyl ester (I) with PBr3 in ethyl ether gives the corresponding 2-bromomethyl derivative (II), which is condensed with hexadecylthiol (III) by means of triethylamine to afford 2-(hexadecylsulfanyl)-2-propenoic acid ethyl ester (IV). The reduction of (IV) with diisobutylaluminum hydride (DIBAL) yields 3-(hexadecylsulfanyl)-2-methylene-1-propanol (V), which is methylated with NaH and MeI to the methyl ether (VI). The hydroboration of (VI) with BH3.S(CH3)2 followed by oxidation with NaBO3 gives 3-(hexadecylsulfanyl)-2-(methoxymethyl)-1-propanol (VII), which is finally phosphorylated with PCl3 and condensed with choline p-toluenesulfonate (VIII).

参考文献中间体

合成目标

【1】 Reddy, K.C.; Byun, H.S.; Bittman, R.; Antitumor ether lipids: An improved synthesis of ilmofosine and an enantioselective synthesis of an ilmofosine analog. Tetrahedron Lett 1994, 35, 17, 2679.

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)	11327	ethyl 2-(hydroxymethyl)acrylate	10029-04-6	C₆H₁₀O₃	详情	详情
(II)	11328	ethyl 2-(bromomethyl)acrylate	17435-72-2	C₆H₉BrO₂	详情	详情
(III)	41266	1-hexadecanethiol; hexadecylhydrosulfide	2917-26-2	C₁₆H₃₄S	详情	详情
(IV)	11329	ethyl 2-[(hexadecylsulfanyl)methyl]acrylate		C₂₂H₄₂O₂S	详情	详情
(V)	11330	2-[(Hexadecylsulfanyl)methyl]-2-propen-1-ol		C₂₀H₄₀OS	详情	详情
(VI)	11331	2-[(Hexadecylsulfanyl)methyl]-2-propenyl methyl ether; 3-(Hexadecylsulfanyl)-2-(methoxymethyl)-1-propene		C₂₁H₄₂OS	详情	详情
(VII)	11332	3-(Hexadecylsulfanyl)-2-(methoxymethyl)-1-propanol		C₂₁H₄₄O₂S	详情	详情
(VIII)	11333	N,N,N-Trimethyl-2-[(phenylsulfonyl)oxy]-1-ethanaminium chloride		C₁₁H₁₈ClNO₃S	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 reaction of 2-(hydroxymethyl)propenoic acid ethyl ester (I) with PBr3 and then with hexadecyl mercaptane (II) and TEA gives 2-(hexadecylsulfanylmethyl)propenoic acid methyl ester (III), which is reduced with DIBAL in THF to the corresponding carbinol (IV). The methylation of (IV) with methyl iodide and NaH in THF affords the methyl ether (V), which is hydroxylated at the double bond with BH3/Me2S and NaBO3 providing 3-(hexadecylsulfanyl)-2-(methoxymethyl)-1-propanol (VI). Finally this compound is treated with POCl3 and TEA in chloroform and condensed with choline tosylate (VII) to furnish the target phosphorylcholine derivative.

参考文献中间体

合成目标

【1】 Bittman, R.; Lohmeyer, M.; Antitumor ether lipids and alkylphosphocholines. Drugs Fut 1994, 19, 11, 1021.
【2】 Reddy, K.C.; Byun, H.S.; Bittman, R.; Antitumor ether lipids: An improved synthesis of ilmofosine and an enantioselective synthesis of an ilmofosine analog. Tetrahedron Lett 1994, 35, 17, 2679.

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)	11327	ethyl 2-(hydroxymethyl)acrylate	10029-04-6	C₆H₁₀O₃	详情	详情
(II)	41266	1-hexadecanethiol; hexadecylhydrosulfide	2917-26-2	C₁₆H₃₄S	详情	详情
(III)	11329	ethyl 2-[(hexadecylsulfanyl)methyl]acrylate		C₂₂H₄₂O₂S	详情	详情
(IV)	11330	2-[(Hexadecylsulfanyl)methyl]-2-propen-1-ol		C₂₀H₄₀OS	详情	详情
(V)	11331	2-[(Hexadecylsulfanyl)methyl]-2-propenyl methyl ether; 3-(Hexadecylsulfanyl)-2-(methoxymethyl)-1-propene		C₂₁H₄₂OS	详情	详情
(VI)	11332	3-(Hexadecylsulfanyl)-2-(methoxymethyl)-1-propanol		C₂₁H₄₄O₂S	详情	详情
(VII)	41265	2-hydroxy-N,N,N-trimethyl-1-ethanaminium 4-methylbenzenesulfonate		C₁₂H₂₁NO₄S	详情	详情

合成路线3

该中间体在本合成路线中的序号：(XLII)

Condensation of the bicyclic oxazoline (XV) with 2-(chloromethyl)acrylic acid ethyl ester (XLI) - obtained by treatment of the hydroxymethyl analogue (XLII) with SOCl2 - in dimethylacetamide gives the aduct (XLIII), which is treated first with hydroquinone and Na2CO3 in water and then with H2 over Pd/Al2O3 in the same solvent to provide 2,2'-anhydro-b-L-thymidine (XLIV). Reaction of compound (XLIV) with acetyl bromide in DMF/AcOEt yields 2'-bromo-3',5'-di-O-acetyl-b-L-thymidine (XLV), which is debrominated with H2 over Pd/Al2O3.to afford the 2'-deoxynucleoside (XLVI). Finally, this compound is deacetylated by means of NH3 in MeOH.

参考文献中间体

合成目标

【1】 Sorbera, L.A.; Castañer, J.; Castañer, R.M.; Bayes, M.; Telbivudine. Drugs Fut 2003, 28, 9, 870.
【2】 Suzuki, T.; Iizuka, H.; Togashi, K. (Mitsui Chemicals, Inc.); L-Nucleic acid derivs. and processes for the synthesis thereof. EP 1348712; JP 2002241390; WO 0244194 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XV)	56918	(3aS,5S,6S,6aR)-5-(hydroxymethyl)-2-iminohexahydrofuro[2,3-d][1,3]oxazol-6-ol		C₆H₁₀N₂O₄	详情	详情
(XLI)	62924	ethyl 2-(chloromethyl)acrylate		C₆H₉ClO₂	详情	详情
(XLII)	11327	ethyl 2-(hydroxymethyl)acrylate	10029-04-6	C₆H₁₀O₃	详情	详情
(XLIII)	62923	ethyl 2-{[(3aS,5S,6S,6aR)-6-hydroxy-5-(hydroxymethyl)-2-iminotetrahydrofuro[2,3-d][1,3]oxazol-3(2H)-yl]methyl}acrylate		C₁₂H₁₈N₂O₆	详情	详情
(XLIV)	62927	(2S,3S,3aR,9aS)-3-hydroxy-2-(hydroxymethyl)-7-methyl-2,3,3a,9a-tetrahydro-6H-furo[2',3':4,5][1,3]oxazolo[3,2-a]pyrimidin-6-one		C₁₀H₁₂N₂O₅	详情	详情
(XLV)	12213	[(2R,3R,4R,5R)-3-(acetoxy)-4-bromo-5-[5-methyl-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]tetrahydro-2-furanyl]methyl acetate		C₁₄H₁₇BrN₂O₇	详情	详情
(XLVI)	62928	{(2S,3R,5S)-3-(acetyloxy)-5-[5-methyl-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]tetrahydro-2-furanyl}methyl acetate		C₁₄H₁₈N₂O₇	详情	详情

Extended Information