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【结 构 式】

【分子编号】51153

【品名】(4-bromo-3-methylphenyl)lithium

【CA登记号】

【 分 子 式 】C7H6BrLi

【 分 子 量 】176.96964

【元素组成】C 47.51% H 3.42% Br 45.15% Li 3.92%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(II)

Lithiation of 2,5-dibromotoluene (I) with n-butyllithium at -75 C produced a mixture of 5-lithio (II) and 2-lithio (III) toluenes. Addition of this mixture to N-Boc-4-piperidone (IV) at low temperature provided the desired carbinol (V) and the corresponding 2-tolyl regioisomer, which were separated by flash chromatography (1). Alternatively, carbinol (V) was obtained by regioselective metallation of 2-bromo-5-iodotoluene (VI) and then addition to N-Boc-4-piperidone (IV). Dehydration of carbinol (V) with concomitant N-Boc group cleavage under acidic conditions furnished the tetrahydropyridine (VII). This was sulfonylated with methyl chlorosulfonylacetate (VIII) in the presence of either N,O-bis(trimethylsilyl)acetamide or diazabicycloundecene, producing sulfonamide (IX). Suzuki coupling of aryl bromide (IX) with 3-ethoxyphenylboronic acid (X) gave biphenyl (XI). The methyl ester group of (XI) was then condensed with hydroxylamine to afford the title hydroxamic acid.

1 Dack, K.N.; et al.; Design and synthesis of a novel series of matrix metalloproteinase inhibitors with high selectivity for MMP-3. 222nd ACS Natl Meet (Aug 26 2001, Chicago) 2001, Abst MEDI 260.
2 Whitlock, G.A.; Dack, K.N. (Pfizer Inc.); Hydroxamic acid derivs. as matrix metalloprotease (MMP) inhibitors. EP 1036062; JP 2001525396; WO 9929667 .
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) 51152 2,5-Dibromotoluene 615-59-8 C7H6Br2 详情 详情
(II) 51153 (4-bromo-3-methylphenyl)lithium C7H6BrLi 详情 详情
(III) 51154 (4-bromo-2-methylphenyl)lithium C7H6BrLi 详情 详情
(IV) 18620 tert-butyl 4-oxo-1-piperidinecarboxylate;BOC-Piperidone;N-(tert-Butoxycarbonyl)-4-piperidone; N-Boc-4-piperidone 79099-07-3 C10H17NO3 详情 详情
(V) 51155 tert-butyl 4-(4-bromo-3-methylphenyl)-4-hydroxy-1-piperidinecarboxylate C17H24BrNO3 详情 详情
(VI) 51156 2-Bromo-5-iodotoluene C7H6BrI 详情 详情
(VII) 51157 4-(4-bromo-3-methylphenyl)-1,2,3,6-tetrahydropyridine C12H14BrN 详情 详情
(VIII) 51158 methyl 2-(chlorosulfonyl)acetate C3H5ClO4S 详情 详情
(IX) 51159 methyl 2-[[4-(4-bromo-3-methylphenyl)-3,6-dihydro-1(2H)-pyridinyl]sulfonyl]acetate C15H18BrNO4S 详情 详情
(X) 51160 3-Ethoxyphenylboronic acid C8H11BO3 详情 详情
(XI) 51151 2-(5-[[(3R)-3-(dimethylamino)pyrrolidinyl]sulfonyl]-2-propoxyphenyl)-5-[(4-fluorobenzyl)amino]-8-(4-methoxybenzyl)-3,8-dihydro-4H-pyrazolo[4',3':5,6]pyrido[4,3-d]pyrimidin-4-one C38H41FN8O5S 详情 详情
Extended Information