(E)-4-phenyl-2-buten-1-ol -Drug Synthesis Database

【结构式】

【分子编号】32806

【品名】(E)-4-phenyl-2-buten-1-ol

【CA登记号】

【分子式】C₁₀H₁₂O

【分子量】148.20468

【元素组成】C 81.04% H 8.16% O 10.8%

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：(II)

The Grignard reaction of vinyloxirane (I) with phenylmagnesium bromide and CuCN in THF gives 4-phenyl-2-buten-1-ol (II), which is submitted to a Sharpless epoxidation with t-BuOOH and Ti(Oi-Pr)4 in dichloromethane in the presence of (-)-diethyl tartrate [(-)-DET] yielding the chiral epoxide (III). The reaction of (III) with Ti(Oi-Pr)2(N3)2 in refluxing benzene affords the 3(S)-azido-4-phenylbutane-1,2(S)-diol (IV), which is epoxidized with 2-acetoxy-2-methylpropionyl chloride (A) and NaOMe in THF to give the chiral azidoepoxide (V). The reaction of (V) with isobutylamine (VI) in hot isopropanol yields the secondary amine (VII), which is condensed with 4-methoxyphenylsulfonyl chloride (VIII) in pyridine affording the sulfonamide (IX). The reduction of the azido group of (IX) with H2 over Pd/C in methanol provides (X) with a primary amino group that is finally condensed with the succinimidinyl carbonate (XI) by means of triethylamine in acetonitrile.

参考文献中间体

合成目标

【1】 Ghosh, A.K.; Kincaid, J.F.; Cho, W.; Walters, D.E.; Krishnan, K.; Hussain, K.A.; Koo, Y.; Cho, H.; Rudall, C.; Holland, L.; Buthod, J.; Potent HIV protease inhibitors incorporating high-affinity P2-ligands and (R)-(hydroxyethylamino)sulfonamide isostere. Bioorg Med Chem Lett 1998, 8, 6, 687.
【2】 Hussain, K.A.; Gulnik, S.V.; Ghosh, A.K.; Erickson, J.W. (University of Illinois; US Department of Health & Human Services); Multi-drug resistant retroviral protease inhibitors and associated methods. WO 9967254 .
【3】 Ghosh, A.K.; et al.; Potent HIV protease inhibitors: The development of tetrahydrofuranylglycines as novel P2-ligands and pyrazine amides as P3-ligands. J Med Chem 1993, 36, 16, 2300.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	17616	bromo(phenyl)magnesium; Phenyl Magnesium Bromide	100-58-3	C₆H₅BrMg	详情	详情
(A)	32808	2-chloro-1,1-dimethyl-2-oxoethyl acetate	40635-66-3	C₆H₉ClO₃	详情	详情
(I)	32805	2-vinyloxirane	930-22-3	C₄H₆O	详情	详情
(II)	32806	(E)-4-phenyl-2-buten-1-ol		C₁₀H₁₂O	详情	详情
(III)	32807	[(2R,3S)-3-benzyloxiranyl]methanol	116949-62-3	C₁₀H₁₂O₂	详情	详情
(IV)	14544	(2S,3S)-3-azido-4-phenyl-1,2-butanediol		C₁₀H₁₃N₃O₂	详情	详情
(V)	14547	(1S)-1-[(2S)oxiranyl]-2-phenylethyl azide; (2S)-2-[(1S)-1-azido-2-phenylethyl]oxirane		C₁₀H₁₁N₃O	详情	详情
(VI)	13306	2-Methyl-1-propanamine; Isobutylamine	78-81-9	C₄H₁₁N	详情	详情
(VII)	32809	(2R,3S)-3-azido-1-(isobutylamino)-4-phenyl-2-butanol		C₁₄H₂₂N₄O	详情	详情
(VIII)	15719	4-methoxybenzenesulfonyl chloride	98-68-0	C₇H₇ClO₃S	详情	详情
(IX)	32810	N-[(2R,3S)-3-azido-2-hydroxy-4-phenylbutyl]-N-isobutyl-4-methoxybenzenesulfonamide		C₂₁H₂₈N₄O₄S	详情	详情
(X)	32811	N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N-isobutyl-4-methoxybenzenesulfonamide		C₂₁H₃₀N₂O₄S	详情	详情
(XI)	32812	1-([[(3R,3aS,6aR)hexahydrofuro[2,3-b]furan-3-yloxy]carbonyl]oxy)-2,5-pyrrolidinedione		C₁₁H₁₃NO₇	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XIII)

The reaction of butadiene monooxide (XI) with phenylmagnesium bromide (XII) and CuCN in THF gives trans-4-phenyl-2-buten-1-ol (XIII), which is enantioselectively epoxidated with Ti(O-iPr)4, diethyl D-tartrate and tBu-OOH to yield the (2R,3R)-epoxide (XIV). The reaction of (XIV) with Ti(O-iPr)4 and N3-SiMe3 in refluxing benzene affords the chiral azidodiol (XV), which is epoxidated by means of 2-acetoxyisobutyryl chloride (AcBCl) and NaOMe in THF to provide the chiral azidoepoxide (XVI) (1). Opening of the epoxide ring of (XVI) with isobutylamine (XVII) in hot isopropanol gives the secondary amine (XVIII), which is acylated with 4-aminophenylsulfonyl chloride (XIX) and pyridine in dichloromethane to yield the corresponding sulfonamide (XX). The reduction of the azido group of (XX) with H2 over Pd/C in THF/methanol/HOAc affords the expected primary amine (XXI), which is finally condensed with the already reported intermediate (X) in dichloromethane to provide the target carbamate.

参考文献中间体

合成目标

【1】 Ghosh, A.K.; Kincaid, J.F.; Cho, W.; Walters, D.E.; Krishnan, K.; Hussain, K.A.; Koo, Y.; Cho, H.; Rudall, C.; Holland, L.; Buthod, J.; Potent HIV protease inhibitors incorporating high-affinity P2-ligands and (R)-(hydroxyethylamino)sulfonamide isostere. Bioorg Med Chem Lett 1998, 8, 6, 687.
【2】 Hussain, K.A.; Gulnik, S.V.; Ghosh, A.K.; Erickson, J.W. (University of Illinois; US Department of Health & Human Services); Multi-drug resistant retroviral protease inhibitors and associated methods. WO 9967254 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(X)	32812	1-([[(3R,3aS,6aR)hexahydrofuro[2,3-b]furan-3-yloxy]carbonyl]oxy)-2,5-pyrrolidinedione		C₁₁H₁₃NO₇	详情	详情
(XI)	32805	2-vinyloxirane	930-22-3	C₄H₆O	详情	详情
(XII)	17616	bromo(phenyl)magnesium; Phenyl Magnesium Bromide	100-58-3	C₆H₅BrMg	详情	详情
(XIII)	32806	(E)-4-phenyl-2-buten-1-ol		C₁₀H₁₂O	详情	详情
(XIV)	53549	[(2R,3R)-3-benzyloxiranyl]methanol	n/a	C₁₀H₁₂O₂	详情	详情
(XV)	14544	(2S,3S)-3-azido-4-phenyl-1,2-butanediol		C₁₀H₁₃N₃O₂	详情	详情
(XVI)	14547	(1S)-1-[(2S)oxiranyl]-2-phenylethyl azide; (2S)-2-[(1S)-1-azido-2-phenylethyl]oxirane		C₁₀H₁₁N₃O	详情	详情
(XVII)	13306	2-Methyl-1-propanamine; Isobutylamine	78-81-9	C₄H₁₁N	详情	详情
(XVIII)	32809	(2R,3S)-3-azido-1-(isobutylamino)-4-phenyl-2-butanol		C₁₄H₂₂N₄O	详情	详情
(XIX)	53550	4-aminobenzenesulfonyl chloride	98-62-4	C₆H₆ClNO₂S	详情	详情
(XX)	53551	4-amino-N-[(2R,3S)-3-azido-2-hydroxy-4-phenylbutyl]-N-isobutylbenzenesulfonamide	n/a	C₂₀H₂₇N₅O₃S	详情	详情
(XXI)	45533	4-amino-N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N-isobutylbenzenesulfonamide		C₂₀H₂₉N₃O₃S	详情	详情

Extended Information