6-(4-phenylbutoxy)-1-hexanamine; 6-(4-phenylbutoxy)hexylamine -Drug Synthesis Database

【结构式】

【分子编号】62577

【品名】6-(4-phenylbutoxy)-1-hexanamine; 6-(4-phenylbutoxy)hexylamine

【CA登记号】

【分子式】C₁₆H₂₇NO

【分子量】249.39652

【元素组成】C 77.06% H 10.91% N 5.62% O 6.42%

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)

The enantioselective reduction of the phenacyl bromide (I) by means of a culture of Rhodotolule rubra in water gives the a(R)-hydroxy enantiomer (II), which is treated with K2CO3 in refluxing ethanol to yield the chiral epoxide (III). The condensation of (III) with 6-(4-phenylbutoxy)hexylamine (IV) by means of N,O-bis(trimethylsilyl)acetamide (TMSA) in hot DMSO affords the precursor (V), which is finally deprotected by means of HCl in water to provide the target (R)-salmeterol.

参考文献中间体

合成目标

【1】 Goswami, J.; et al.; A conventient stereoselective synthesis of (R)-(-)-denopamine and (R)-(-)-salmeterol. Tetrahedron Asymmetry 2001, 12, 24, 3343.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	62574	1-(4H-1,3-benzodioxin-6-yl)-2-bromo-1-ethanone	C₁₀H₉BrO₃	详情	详情
(II)	62575	(1R)-1-(4H-1,3-benzodioxin-6-yl)-2-bromo-1-ethanol	C₁₀H₁₁BrO₃	详情	详情
(III)	62576	6-[(2R)oxiranyl]-4H-1,3-benzodioxine	C₁₀H₁₀O₃	详情	详情
(IV)	62577	6-(4-phenylbutoxy)-1-hexanamine; 6-(4-phenylbutoxy)hexylamine	C₁₆H₂₇NO	详情	详情
(V)	62578	(1R)-1-(4H-1,3-benzodioxin-6-yl)-2-{[6-(4-phenylbutoxy)hexyl]amino}-1-ethanol	C₂₆H₃₇NO₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

The enantioselective reduction of the phenacyl bromide (I) by means of a culture of Rhodotolule rubra in water gives the a(R)-hydroxy enantiomer (II), which is treated with K2CO3 in refluxing ethanol to yield the chiral epoxide (III). The condensation of (III) with 6-(4-phenylbutoxy)hexylamine (IV) by means of N,O-bis(trimethylsilyl)acetamide (TMSA) in hot DMSO affords the benzylated precursor (V), which is finally deprotected by means of H2,Pd/C in water to provide the target (R)-salmeterol.

参考文献中间体

合成目标

【1】 Goswami, J.; et al.; A conventient stereoselective synthesis of (R)-(-)-denopamine and (R)-(-)-salmeterol. Tetrahedron Asymmetry 2001, 12, 24, 3343.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	62579	1-[4-(benzyloxy)-3-(hydroxymethyl)phenyl]-2-bromo-1-ethanone	C₁₆H₁₅BrO₃	详情	详情
(II)	62580	(1R)-1-[4-(benzyloxy)-3-(hydroxymethyl)phenyl]-2-bromo-1-ethanol	C₁₆H₁₇BrO₃	详情	详情
(III)	62581	{2-(benzyloxy)-5-[(2R)oxiranyl]phenyl}methanol	C₁₆H₁₆O₃	详情	详情
(IV)	62577	6-(4-phenylbutoxy)-1-hexanamine; 6-(4-phenylbutoxy)hexylamine	C₁₆H₂₇NO	详情	详情
(V)	62582	(1R)-1-[4-(benzyloxy)-3-(hydroxymethyl)phenyl]-2-{[6-(4-phenylbutoxy)hexyl]amino}-1-ethanol	C₃₂H₄₃NO₄	详情	详情

合成路线3

该中间体在本合成路线中的序号：(VIII)

The reaction of 6-(4-phenylbutoxy)hexyl bromide (VI) with NaN3 in DMF gives The azido derivative (VII), which is reduced with LiAlH4 to yield the primary amine (VIII). The reductive alkylation of (VIII) by means of benzaldehyde and NaBH4 affords the benzylamine (IX), which is condensed with the chiral epoxide (V) in refluxing THF to provide the chiral hydroxyamine (X). The reduction of the ester group of (X) with LiAlH4 leads to the hydroxymethyl compound (XI), which is finally fully debenzylated by means of H2 over Pd/C to give rise to the target (R)-salmeterol.

参考文献中间体

合成目标

【1】 Hett, R.; et al.; Enantioselective synthesis of salmeterol via asymmetric borane reduction. Tetrahedron Lett 1994, 35, 50, 9375.

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)	62585	methyl 2-(benzyloxy)-5-[(2R)oxiranyl]benzoate		C₁₇H₁₆O₄	详情	详情
(VI)	31479	1-[4-[(6-bromohexyl)oxy]butyl]benzene; 6-bromohexyl-4-phenylbutyl ether; 6-Bromohexyloxybutylbenzene	94749-73-2	C₁₆H₂₅BrO	详情	详情
(VII)	62586	1-{4-[(6-azidohexyl)oxy]butyl}benzene; 6-azidohexyl 4-phenylbutyl ether		C₁₆H₂₅N₃O	详情	详情
(VIII)	62577	6-(4-phenylbutoxy)-1-hexanamine; 6-(4-phenylbutoxy)hexylamine		C₁₆H₂₇NO	详情	详情
(IX)	35837	N-benzyl-6-(4-phenylbutoxy)-1-hexanamine; N-benzyl-N-[6-(4-phenylbutoxy)hexyl]amine		C₂₃H₃₃NO	详情	详情
(X)	62587	methyl 2-(benzyloxy)-5-((1R)-2-{benzyl[6-(4-phenylbutoxy)hexyl]amino}-1-hydroxyethyl)benzoate		C₄₀H₄₉NO₅	详情	详情
(XI)	62588	(1R)-1-[4-(benzyloxy)-3-(hydroxymethyl)phenyl]-2-{benzyl[6-(4-phenylbutoxy)hexyl]amino}-1-ethanol		C₃₉H₄₉NO₄	详情	详情

Extended Information