n-Valeraldehyde; Pentanal -Drug Synthesis Database

【结构式】

【分子编号】13409

【品名】n-Valeraldehyde; Pentanal

【CA登记号】110-62-3

【分子式】C₅H₁₀O

【分子量】86.1338

【元素组成】C 69.72% H 11.7% O 18.58%

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：(IV)

A new synthesis of rosaprostol has been developed: Reaction of 3-(dimethoxyphosphorylmethyl)-2-cyclopenten-1-one (I) with 7-iodoheptanoic acid methyl ester (II) by means of NaH in DMSO gives the C-2 alkylated cyclopentenone (III), which is condensed with pentanal (IV) by means of NaOMe in methanol to yield the dienone (V). Reduction of the double bonds of (V) with H2 over PtO2 in acetic acid affords a mixture of the cis- and trans-cyclopentanones (VI) and (VII) which, without isolation, is submitted to epimerization with TsOH in methanol to furnish almost quantitatively the desired trans-isomer (VII). The hydrolysis of the methyl ester of (VII) with NaOH in dioxane/water gives the corresponding carboxylic acid (VIII), which is finally hydrogenated with NaBH4 in methanol.

参考文献中间体

合成目标

【1】 Jankowiak, A.; Mikina, M.; Mikoajczyk, M.; Mphaphlele, M.J.; A new synthesis of racemic rosaprostol. Synthesis 2000, 8, 1075.

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)	48222	dimethyl (3-oxo-1-cyclopenten-1-yl)methylphosphonate		C₈H₁₃O₄P	详情	详情
(II)	48223	methyl 7-iodoheptanoate		C₈H₁₅IO₂	详情	详情
(III)	48224	methyl 7-[2-[(dimethoxyphosphoryl)methyl]-5-oxo-1-cyclopenten-1-yl]heptanoate		C₁₆H₂₇O₆P	详情	详情
(IV)	13409	n-Valeraldehyde; Pentanal	110-62-3	C₅H₁₀O	详情	详情
(V)	48225	methyl 7-[2-[(E)-1-hexenyl]-5-oxo-1-cyclopenten-1-yl]heptanoate		C₁₉H₃₀O₃	详情	详情
(VI)	48226	methyl 7-[(1R,2R)-2-hexyl-5-oxocyclopentyl]heptanoate		C₁₉H₃₄O₃	详情	详情
(VII)	48227	methyl 7-[(1S,2R)-2-hexyl-5-oxocyclopentyl]heptanoate		C₁₉H₃₄O₃	详情	详情
(VIII)	23958	7-[(1R,2S)-2-hexyl-5-oxocyclopentyl]heptanoic acid		C₁₈H₃₂O₃	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 hindered base, diisobutylamine, was used in the Stork enamine synthesis of valeraldehyde (I) with allyl bromide to yield the desired aldehyde (II) following acidic hydrolysis and subsequent hydrogenation. Acid-catalyzed annelation of (II) with methyl vinyl ketone provided 4,4-dipropylcyclohex-2-enone which upon hydrogenation gave (III). Piperidine-catalyzed condensation of ethyl cyanoacetate with (III) gave cyanoester (IV). Michael addition of KCN followed by acidic hydrolysis gave diacid (V). Treatment of diacid (V) with acetic anhydride gave desired anhydride (VI), which was condensed with N,N-dimethylaminopropylamine to yield the desired imide (VII). Lithium aluminum hydride reduction of the imide (VII) gave the desired diamine which was treated with anhydrous HCl/ethanol to give the required dihydrochloride salt, SK&F 105685.

参考文献中间体

合成目标

【1】 Curphey, T.J.; Chu, C.C.C.; Hung, J.C.; A study of the alkylation of enamines derived from sterically hindered amines. J Org Chem 1975, 40, 607-14.
【2】 Flaugh, M.E.; Crowell, T.A.; Farlow, D.S.; Acid-catalyzed annelation of alpha-alkyl aldehydes and alpha,beta-unsaturated ketones. A one-pot synthesis of 4,4-dimethyl-2-cyclohexen-1-one. J Org Chem 1980, 45, 5399-400.
【3】 Schwartz, D.A.; Badger, A.M.; SK&F-105685. Drugs Fut 1991, 16, 9, 815.

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)	13409	n-Valeraldehyde; Pentanal	110-62-3	C₅H₁₀O	详情	详情
(II)	13410	2-Propylpentanal		C₈H₁₆O	详情	详情
(III)	13411	4,4-Dipropylcyclohexanone	123018-62-2	C₁₂H₂₂O	详情	详情
(IV)	13412	ethyl 2-cyano-2-(4,4-dipropylcyclohexylidene)acetate		C₁₇H₂₇NO₂	详情	详情
(V)	13413	1-(Carboxymethyl)-4,4-dipropylcyclohexanecarboxylic acid		C₁₅H₂₆O₄	详情	详情
(VI)	13414	8,8-Dipropyl-2-oxaspiro[4.5]decane-1,3-dione		C₁₅H₂₄O₃	详情	详情
(VII)	13415	2-[3-Ddimethylamino)propyl]-8,8-dipropyl-2-azaspiro[4.5]decane-1,3-dione		C₂₀H₃₆N₂O₂	详情	详情

合成路线3

该中间体在本合成路线中的序号：(XXII)

5-Hydroxy-4-propyl-2-furanone (V) is obtained by aldol condensation of glyoxylic acid (XXI) with valeraldehyde (XXII) in the presence of morpholine in heptane, followed by cyclization of the intermediate aldehyde acid under acidic conditions .
Preparation of iodoacyl chloride (VIII) starts with the conjugate addition of propylmagnesium bromide (XXIV) to 2-furanone (XXIII) in the presence of CuI and TMSCl in ethyl ether to produce 4-propylbutyrolactone (XXV), which undergoes lactone ring opening by means of iodotrimethylsilane in CH2Cl2, affording 3-(iodomethyl)hexanoic acid (XXVI), and finally, chlorination of acid (XXVI) with SOCl2 in benzene .

参考文献中间体

合成目标

【1】 Surtees, J., Lurquin, F., Diouf, O. (UCB SA). Process for preparing 2-oxo-1-pyrrolidine derivatives. CA 2538938, EP 1667967, JP 2007515387, US 2007100150, US 7629474, WO 2005028435.
【2】 Kenda, B.M., Matagne, A.C., Talaga, P.E. et al. Discovery of 4-substituted pyrrolidone butanamides as new agents with significant antiepileptic activity. J Med Chem 2004, 47(3): 530-49.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(V)	58391	5-hydroxy-4-propyl-2(5H)-furanone；5-hydroxy-4-propyl-2-furanone	78920-10-2	C₇H₁₀O₃	详情	详情
(VIII)	69031	3-(iodomethyl)hexanoyl chloride		C₇H₁₂ClIO	详情	详情
(XXI)	15618	2-Oxoacetic acid; Glyoxylic Acid	298-12-4	C₂H₂O₃	详情	详情
(XXII)	13409	n-Valeraldehyde; Pentanal	110-62-3	C₅H₁₀O	详情	详情
(XXIII)	19267	2(5H)-furanone；furan-2(5H)-one；2-Buten-1,4-olide	497-23-4	C₄H₄O₂	详情	详情
(XXIV)	10790	Bromo(propyl)magnesium；bromopropylMagnesium；4-propylbutyrolactone；propylmagnesiumbromide；n-propylmagnesium bromide；Bromopropylmagnesium;	927-77-5	C₃H₇BrMg	详情	详情
(XXV)	69043	4-propyldihydrofuran-2(3H)-one		C₇H₁₂O₂	详情	详情
(XXVI)	69044	3-(iodomethyl)hexanoic acid		C₇H₁₃IO₂	详情	详情

Extended Information