4-(2-chloro-5-nitrobenzyl)phenyl methyl ether; 1-chloro-2-(4-methoxybenzyl)-4-nitrobenzene -Drug Synthesis Database

【结构式】

【分子编号】59707

【品名】4-(2-chloro-5-nitrobenzyl)phenyl methyl ether; 1-chloro-2-(4-methoxybenzyl)-4-nitrobenzene

【CA登记号】

【分子式】C₁₄H₁₂ClNO₃

【分子量】277.70692

【元素组成】C 60.55% H 4.36% Cl 12.77% N 5.04% O 17.28%

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：(IV)

Treatment of 2-chloro-5-nitrobenzoic acid (I) with PCl5 provides acid chloride (II), which is then condensed with anisole in the presence of AlCl3 to furnish the benzophenone (III). Alternatively, ketone (III) is prepared by Friedel-Crafts condensation of 2-chloro-5-nitrobenzoic acid (I) with anisole in hot polyphosphoric acid. Reduction of ketone (III) employing triethylsilane and trifluoromethanesulfonic acid gives rise to diphenylmethane derivative (IV)

参考文献中间体

合成目标

【1】 Manning, R.E.; Tremont, S.J.; Glenn, K.C.; Keller, B.T. (Pharmacia Corp.); Combination therapy for the prophylaxis and treatment of hyperlipidemic conditions and disorders. WO 0168096 .

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)	10188	2-Chloro-5-nitrobenzoic acid	2516-96-3	C₇H₄ClNO₄	详情	详情
(II)	10189	2-Chloro-5-nitrobenzoyl chloride	25784-91-2	C₇H₃Cl₂NO₃	详情	详情
(III)	59706	(2-chloro-5-nitrophenyl)(4-methoxyphenyl)methanone		C₁₄H₁₀ClNO₄	详情	详情
(IV)	59707	4-(2-chloro-5-nitrobenzyl)phenyl methyl ether; 1-chloro-2-(4-methoxybenzyl)-4-nitrobenzene		C₁₄H₁₂ClNO₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

Reduction of malonate (V) with LiAlH4 affords diol (VI). Reaction of diol (VI) with an acetic acid solution of hydrobromic acid, followed by acidic hydrolysis of the generated acetate ester, furnishes bromo alcohol (VII). This is oxidized to the bromo aldehyde (VIII) employing either DMSO and SO3-pyridine complex or NaOCl in the presence of TEMPO and KBr. Treatment of aryl chloride (IV) with sodium sulfide, followed by addition of bromo aldehyde (VIII) leads to the sulfide adduct (IX). After protection of the aldehyde group of (IX) as the dimethyl acetal (X) by means of trimethyl orthoformate and p-toluenesulfonic acid, the sulfide function of (X) is oxidized to sulfone (XI) with peracetic acid. Acetal hydrolysis in (XI) under acidic conditions then gives aldehyde (XII). Reductive alkylation of the nitro compound (XII) by catalytic hydrogenation in the presence of Pd/C and formaldehyde yields the dimethylamino derivative (XIII)

参考文献中间体

合成目标

【1】 Manning, R.E.; Tremont, S.J.; Glenn, K.C.; Keller, B.T. (Pharmacia Corp.); Combination therapy for the prophylaxis and treatment of hyperlipidemic conditions and disorders. WO 0168096 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IV)	59707	4-(2-chloro-5-nitrobenzyl)phenyl methyl ether; 1-chloro-2-(4-methoxybenzyl)-4-nitrobenzene		C₁₄H₁₂ClNO₃	详情	详情
(V)	59708	ethyl 2-butyl-2-(2-methoxyacetyl)hexanoate		C₁₅H₂₈O₄	详情	详情
(VI)	59709	2,2-dibutyl-1,3-propanediol;2,2-DIBUTYLPROPANE-1,3-DIOL;2-N-BUTYL-2-(HYDROXYMETHYL)-1-HEXANOL	24765-57-9	C₁₁H₂₄O₂	详情	详情
(VII)	59710	2-(bromomethyl)-2-butyl-1-hexanol		C₁₁H₂₃BrO	详情	详情
(VIII)	59712	2-(bromomethyl)-2-butylhexanoic acid		C₁₁H₂₁BrO₂	详情	详情
(IX)	59711	2-butyl-2-({[2-(4-methoxybenzyl)-4-nitrophenyl]sulfanyl}methyl)hexanal		C₂₅H₃₃NO₄S	详情	详情
(X)	59713	4-(2-{[2-butyl-2-(dimethoxymethyl)hexyl]sulfanyl}-5-nitrobenzyl)phenyl methyl ether; 1-{[2-butyl-2-(dimethoxymethyl)hexyl]sulfanyl}-2-(4-methoxybenzyl)-4-nitrobenzene		C₂₇H₃₉NO₅S	详情	详情
(XI)	59714	[2-butyl-2-(dimethoxymethyl)hexyl][2-(4-methoxybenzyl)-4-nitrophenyl]dioxo-lambda~6~-sulfane; 2-butyl-2-(dimethoxymethyl)hexyl 2-(4-methoxybenzyl)-4-nitrophenyl sulfone		C₂₇H₃₉NO₇S	详情	详情
(XII)	59716	2-butyl-2-({[2-(4-methoxy-2-methylbenzyl)-4-nitrophenyl]sulfonyl}methyl)hexanal		C₂₆H₃₅NO₆S	详情	详情
(XIII)	59715	2-butyl-2-({[4-(dimethylamino)-2-(4-methoxybenzyl)phenyl]sulfonyl}methyl)hexanal		C₂₇H₃₉NO₄S	详情	详情

Extended Information