1-amino-1-(3,4-difluorophenyl)-2-propanol -Drug Synthesis Database

【结构式】

【分子编号】43321

【品名】1-amino-1-(3,4-difluorophenyl)-2-propanol

【CA登记号】

【分子式】C₉H₁₁F₂NO

【分子量】187.1892864

【元素组成】C 57.75% H 5.92% F 20.3% N 7.48% O 8.55%

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：(VI)

The addition of ethylmagnesium bromide to 3,4-difluorobenzaldehyde (I) gave alcohol (II), which was oxidized to ketone (III) by using pyridinium chlorochromate. Treatment of (III) with iodobenzene diacetate in methanolic KOH produced the hydroxy ketone (IV). This was converted to oxime (V) and subsequently reduced with LiAlH4, yielding amino alcohol (VI) as a mixture of diastereoisomers. The mixture of amino alcohols (VI) was treated with Boc2O to afford carbamate (VII), which was then cyclized in the presence of NaH in THF. The resulting diastereomeric mixture of oxazolidinones (VIII) was first separated by column chromatography, and the racemic trans-isomer was then resolved by means of chiral HPLC to provide the required (+)-trans-oxazolidine (IX).

参考文献中间体

合成目标

【1】 Broten, T.P.; Nichtberger, S.A.; Siegl, P.K.S. (Merck & Co., Inc.); Combination therapy for the treatment of benign prostatic hyperplasia. WO 9948530 .
【2】 Marzabadi, M.R.; Wong, W.C.; Gluchowski, C.; Tian, D.; Nagarathnam, D.; Lagu, B.; Dhar, T.G.M.; Jeon, Y.T. (Synaptic Pharmaceutical Corp.); Heterocyclic substd. piperidines and uses thereof. EP 0988295; WO 9857940 .

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)	26654	3,4-difluorobenzaldehyde	34036-07-2	C₇H₄F₂O	详情	详情
(II)	43317	1-(3,4-difluorophenyl)-1-propanol		C₉H₁₀F₂O	详情	详情
(III)	43318	1-(3,4-difluorophenyl)-1-propanone	23384-72-7	C₉H₈F₂O	详情	详情
(IV)	43319	1-(3,4-difluorophenyl)-2-hydroxy-1-propanone		C₉H₈F₂O₂	详情	详情
(V)	43320	1-(3,4-difluorophenyl)-2-hydroxy-1-propanone oxime		C₉H₉F₂NO₂	详情	详情
(VI)	43321	1-amino-1-(3,4-difluorophenyl)-2-propanol		C₉H₁₁F₂NO	详情	详情
(VII)	43322	tert-butyl 1-(3,4-difluorophenyl)-2-hydroxypropylcarbamate		C₁₄H₁₉F₂NO₃	详情	详情
(VIII)	43323	4-(3,4-difluorophenyl)-5-methyl-1,3-oxazolidin-2-one		C₁₀H₉F₂NO₂	详情	详情
(IX)	43324	(4S,5S)-4-(3,4-difluorophenyl)-5-methyl-1,3-oxazolidin-2-one		C₁₀H₉F₂NO₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VI)

In an alternative procedure, 3,4-difluorobenzylamine (X) was condensed with benzophenone in the presence of a catalytic amount of boron trifluoride etherate to afford imine (XI). After deprotonation of (XI) with tert-butyllithium, its condensation with acetaldehyde produced a protected amino alcohol, which was then deprotected by treatment with O-methyl hydroxylamine. The resulting amino alcohol (VI) was converted to oxazolidine (IX) by the same method as above.

参考文献中间体

合成目标

【1】 Tian, D.; Jeon, Y.; Lagu, B.; et al.; De novo design of a novel oxazolidinone analogue as a potent and selective alpha1A adrenergic receptor antagonist with high oral bioavailability. J Med Chem 2000, 43, 15, 2775.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VI)	43321	1-amino-1-(3,4-difluorophenyl)-2-propanol		C₉H₁₁F₂NO	详情	详情
(X)	43325	3,4-difluorobenzylamine; (3,4-difluorophenyl)methanamine	72235-53-1	C₇H₇F₂N	详情	详情
(XI)	43326	N-(3,4-difluorobenzyl)-N-(dibenzylene)amine; (3,4-difluorophenyl)-N-(dibenzylene)methanamine		C₂₀H₁₅F₂N	详情	详情

Extended Information