1-octadecanol -Drug Synthesis Database

【结构式】

【分子编号】21494

【品名】1-octadecanol

【CA登记号】112-92-5

【分子式】C₁₈H₃₈O

【分子量】270.49912

【元素组成】C 79.93% H 14.16% O 5.91%

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：(II)

The reaction of (R)-O-benzylglycidol (I) with octadecanol (II) by means of NaH in hot DMF gives (R)-1-(benzyloxy)-3-(octadecyloxy)-2-propanol (III), which is methylated with methyl iodide and NaH in DMF yielding the corresponding methyl ether (IV). The debenzylation of (IV) with H2 over Pd/C in THF affords the primary alcohol (V), which is finally treated with POCl3/pyridine in CHCl3 and condensed with choline tosylate (VI) 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】 Barner, R.; Hirth, G.; Synthese von Glyceryätherphosphatiden. Herstellung von 1-O-octadecyl-2-O-acetyl-sn-glyceryl-3-phosphorylchloline (`Platelet Activating Factor'), des Enantiomeren sowie einiger analoger Verbindungen. Helv Chim Acta 1982, 65, 1059-84.

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)	12350	Benzyl (2R)oxiranylmethyl ether; (2R)-2-[(Benzyloxy)methyl]oxirane	14618-80-5	C₁₀H₁₂O₂	详情	详情
(II)	21494	1-octadecanol	112-92-5	C₁₈H₃₈O	详情	详情
(III)	41263	(2R)-1-(benzyloxy)-3-(octadecyloxy)-2-propanol		C₂₈H₅₀O₃	详情	详情
(IV)	41264	1-([[(2R)-2-methoxy-3-(octadecyloxy)propyl]oxy]methyl)benzene; benzyl (2R)-2-methoxy-3-(octadecyloxy)propyl ether		C₂₉H₅₂O₃	详情	详情
(V)	40717	(2S)-2-methoxy-3-(octadecyloxy)-1-propanol		C₂₂H₄₆O₃	详情	详情
(VI)	41265	2-hydroxy-N,N,N-trimethyl-1-ethanaminium 4-methylbenzenesulfonate		C₁₂H₂₁NO₄S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

Acetylation of 1-beta-D-arabinofuranosylcytosine 5'-monophosphate (I) with acetic anhydride gives acetylated compound (II), which is treated with tosyl chloride and stearyl alcohol to synthesize stearyl ester (IV). Stearyl ester (IV) is deacetylated and converted to sodium salt.

参考文献中间体

合成目标

【1】 Takahashi, K.; Kodama, K.; YNK01. Drugs Fut 1989, 14, 11, 1056.

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)	21492	[5-[4-amino-2-oxo-1(2H)-pyrimidinyl]-3,4-dihydroxytetrahydro-2-furanyl]methyl dihydrogen phosphate	63-37-6	C₉H₁₄N₃O₈P	详情	详情
(II)	21493	2'-O,3'-O,N4-Triacetyl-1-(5'-O-phosphono-beta-D-arabinosyl)cytosine bis(tributylammonium) salt		C₃₈H₇₄N₅O₁₁P	详情	详情
(III)	21494	1-octadecanol	112-92-5	C₁₈H₃₈O	详情	详情
(IV)	21495	N,N-dibutyl-1-butanaminium ([3,4-bis(acetoxy)-5-[4-(methoxyamino)-2-oxo-1(2H)-pyrimidinyl]tetrahydro-2-furanyl]methoxy)(octadecyloxy)oxophosphoranolate		C₄₄H₈₃N₄O₁₁P	详情	详情

合成路线3

该中间体在本合成路线中的序号：(III)

Perifosine was synthesized via a two-step process. In the first step, phosphorus oxytrichloride (I) was reacted with 4-hydroxy-1-methylpiperidine hydrochloride (II) in dichloromethane at room temperature using pyridine as auxiliary base. The resulting intermediate, without isolation, was reacted with octadecanol (III) to yield desmethyl perifosine (IV). Desmethyl perifosine was purified by recrystallization prior to methylation. The second step consisted of the methylation of desmethyl perifosine (IV), which was carried out with p-toluenesulfonic acid methyl ester in boiling ethanol using potassium carbonate as base. The crude perifosine solution that was obtained after filtration of the cooled reaction mixture was treated with ion exchange resin in order to remove remaining salts and ionic by-products. Pure perifosine was obtained after evaporation and crystallization.

参考文献中间体

合成目标

【1】 Eibl, H.; Engel, J.; Synthesis of hexadecylphosphocholine (miltefosine). Alkylphophocholines: New drugs in cancer therapy. Prog Exp Tumor Res 1992, 34, 1-5.
【2】 Engel, J.; Hilgard, P.; Nossner, G.; Voss, V.; Traiser, M.; Klenner, T.; Kutscher, B.; Perifosine. Drugs Fut 2000, 25, 12, 1257.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	23403	Methyl p-toluenesulfonate; Methyl 4-methylbenzenesulfonate; Methyl 4-toluenesulfonate	80-48-8	C₈H₁₀O₃S	详情	详情
(I)	42493	Phosphoryl chloride; Phosphorus Oxychloride; Phosphorus (V) trichloride oxide	10025-87-3	Cl₃OP	详情	详情
(II)	42494	4-hydroxy-1-methylpiperidinium chloride		C₆H₁₄ClNO	详情	详情
(III)	21494	1-octadecanol	112-92-5	C₁₈H₃₈O	详情	详情
(IV)	42495	4-[[chloro(octadecyloxy)phosphoryl]oxy]-1-methylpiperidinium chloride		C₂₄H₅₀Cl₂NO₃P	详情	详情

Extended Information